Angiogenesis

Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma

96 | Feb 15 2024

The comprehensive analysis of protein and phosphorylation signatures in cholangiocarcinoma revealed the PRKD family's pivotal role, highlighting their potential as novel treatment targets validated by the inhibitory effects of 1-naphthyl PP1 on CCA cell proliferation, migration, and invasion. [Read the Full Post]

Frailty and risk of serious infections in patients with rheumatoid arthritis treated with biologic or targeted-synthetic DMARDs

44 | Feb 04 2024

Frailty significantly amplifies the risk of serious infections and hospitalizations in rheumatoid arthritis patients starting biologic or targeted synthetic disease-modifying drugs, emphasizing the crucial need for tailored interventions in higher-risk populations. [Read the Full Post]

Assessing safety concerns of interstitial lung disease associated with antibody-drug conjugates: a real-world pharmacovigilance evaluation of the FDA adverse event reporting system

56 | Jan 29 2024

The identification of significant safety signals for interstitial lung disease associated with several FDA-approved antibody-drug conjugates underscores the critical need for heightened clinician awareness and early patient monitoring, prompting further research and potential adjustments in clinical practice guidelines. [Read the Full Post]

Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial

50 | Jan 29 2024

In HER2-positive breast cancer patients undergoing neoadjuvant dual HER2-targeted therapy, achieving a pathologic complete response or residual cancer burden I in the breast strongly correlates with a high probability of having no residual disease in the axillary lymph nodes, suggesting a potential consideration for omitting axillary surgical staging in future trials for those demonstrating these favorable responses. [Read the Full Post]

Binding Thermodynamics of Fourth-Generation EGFR Inhibitors Revealed by Absolute Binding Free Energy Calculations

45 | Jan 26 2024

Your detailed study on BLU-945 and its analogues' enhanced binding affinities to EGFR mutants sheds critical light on potential mechanisms for combating drug resistance in NSCLC, potentially steering future drug development toward more effective treatments. [Read the Full Post]

Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines

56 | Jan 23 2024

Isolinderalactone demonstrates significant potential as a therapeutic agent for colorectal cancer by inducing G2/M phase arrest, apoptosis, autophagy, and MAPK pathway activation via ROS-mediated signaling in human CRC cells. [Read the Full Post]

Absorption, Metabolism, and Excretion of [14C]-Tolebrutinib After Oral Administration in Humans, Contribution of the Metabolites to Pharmacological Activity

22 | Jan 23 2024

The study on tolebrutinib revealed extensive metabolism generating multiple metabolites, among which metabolite M2, constituting 4% of circulating radioactivity, retained potent inhibition of Bruton's tyrosine kinase akin to the parent compound, suggesting its likely contribution to the drug's pharmacological activity in vivo. [Read the Full Post]

Trastuzumab Deruxtecan in Previously Treated Patients With HER2-Positive Metastatic Breast Cancer: Updated Survival Results From a Phase 2 Trial (DESTINY-Breast01)

23 | Jan 23 2024

The updated analysis of the DESTINY-Breast01 trial underscores the sustained efficacy and generally consistent safety profile of trastuzumab deruxtecan in heavily pretreated patients with HER2-positive metastatic breast cancer, revealing a 62.0% objective response rate, a median overall survival of 29.1 months, and notable treatment-emergent adverse events such as drug-related interstitial lung disease/pneumonitis in 15.8% of patients. [Read the Full Post]

Astragalus polysaccharide ameliorates insulin resistance in HepG2 cells through activating the STAT5/IGF-1 pathway

62 | Jan 21 2024

Astragalus polysaccharide alleviates insulin resistance in HepG2 cells by activating the STAT5/IGF-1 pathway, as evidenced by its restoration of impaired glucose uptake and modulation of IGF-1, IGF-1 receptor, AKT, and STAT5 signaling, findings reinforced by the counteraction of its effects by the STAT5 inhibitor AG490. [Read the Full Post]

Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway

24 | Jan 20 2024

The study demonstrates that bone marrow mesenchymal stem cell-derived exosomes loaded with si-PYCR1 suppress aerobic glycolysis and bladder cancer growth via the PI3K/AKT pathway by targeting EGFR, showcasing a promising therapeutic avenue for the disease. [Read the Full Post]

JAK2 Inhibitor, Fedratinib, Inhibits P-gp Activity and Co-Treatment Induces Cytotoxicity in Antimitotic Drug-Treated P-gp Overexpressing Resistant KBV20C Cancer Cells

35 | Jan 17 2024

Fedratinib's combination with vincristine demonstrates promising cytotoxicity specifically in P-glycoprotein-overexpressing drug-resistant cancer cells, suggesting its potential as an effective co-treatment strategy for multidrug-resistant cancers. [Read the Full Post]

Preclinical Characterization of XL092, a Novel Receptor Tyrosine Kinase Inhibitor of MET, VEGFR2, AXL, and MER

43 | Jan 15 2024

XL092, a multi-receptor tyrosine kinase inhibitor, exhibits potent antitumor effects and immunomodulatory properties in preclinical models, supporting its potential for clinical evaluation, particularly in combination with immune checkpoint inhibitors. [Read the Full Post]

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

35 | Jan 14 2024

PP121, a dual tyrosine and phosphoinositide kinase inhibitor, demonstrates promising anti-contractile and anti-inflammatory effects in asthma treatment, suggesting its potential as a novel therapeutic compound for managing the condition. [Read the Full Post]

Targeting exon 20 insertion mutations in lung cancer

37 | Jan 14 2024

Recent clinical evidence suggests that targeted therapies like mobocertinib and amivantamab offer promising antitumor activity for patients with EGFR exon 20 insertions in non-small cell lung cancer, while ongoing trials with novel treatments such as DZD9008 and CLN-081 hold potential for further improving survival outcomes in this challenging subset of patients. [Read the Full Post]

Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis

43 | Jan 11 2024

This comprehensive review highlights the evolving landscape of JAK inhibitors in myelofibrosis treatment, emphasizing their varying efficacy in addressing symptoms and the need for further studies to ascertain their precise impact and facilitate more personalized therapeutic approaches. [Read the Full Post]

Polypharmacologic Reprogramming of Tumor-Associated Macrophages toward an Inflammatory Phenotype

50 | Jan 11 2024

This study's establishment of a physiologically relevant in vitro system for TAM polarization unveils BMS-794833 as a potent inhibitor, independent of primary targets but reliant on multiple signaling pathways, offering a promising strategy to reprogram TAMs and suppress cancer growth. [Read the Full Post]

MTX-211 Inhibits GSH Synthesis through Keap1/NRF2/GCLM Axis and Exerts Antitumor Effects in Bladder Cancer

46 | Jan 10 2024

MTX-211 demonstrates promising potential as a therapeutic agent for bladder cancer by inhibiting cell proliferation through the Keap1/NRF2/GCLM signaling pathway and depleting intracellular GSH levels. [Read the Full Post]

In silico and in vitro human metabolism of IOX2, a performance-enhancing doping agent

21 | Jan 10 2024

The study successfully identified thirteen metabolites of IOX2 in human hepatocytes, with hydroxyquinolinyl-IOX2 emerging as a major biomarker, emphasizing the critical role of glucuronide hydrolysis for enhanced detectability in urine, offering valuable insights for anti-doping testing. [Read the Full Post]

HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation

31 | Jan 09 2024

The study unveils a novel relationship where HMGA1 upregulates FGF19, driving pancreatic cancer progression and stroma formation, establishing FGF19 as a potential therapeutic target for a distinct, highly aggressive subset of PDAC. [Read the Full Post]

A pilot study of orelabrutinib treatment in three cases of refractory/relapsed autoimmune haemolytic anaemia/Evans syndrome

42 | Jan 07 2024

The promising response of nine out of twelve patients in our orelabrutinib trial for refractory/relapsed AIHA/Evans Syndrome indicates its potential as a new second-line treatment, offering hope for improved management and quality of life in these conditions. [Read the Full Post]

Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway

103 | Jan 06 2024

Sertad1, upregulated in ischemic conditions, exacerbates neurological injury by activating the CDK4/p-Rb pathway, promoting cell cycle dysregulation and apoptotic cell death. [Read the Full Post]

Sulfatinib, a novel multi-targeted tyrosine kinase inhibitor of FGFR1, CSF1R, and VEGFR1-3, suppresses osteosarcoma proliferation and invasion via dual role in tumor cells and tumor microenvironment

48 | Jan 05 2024

Sulfatinib demonstrates promise in inhibiting osteosarcoma growth while altering the tumor microenvironment towards an immune-activated state, offering potential for clinical translation. [Read the Full Post]

FGF2 positively regulates osteoclastogenesis via activating the ERK-CREB pathway

0 | Jan 01 2024

FGF2 influences bone homeostasis by stimulating osteoclastogenesis via the ERK-CREB pathway, suggesting potential therapeutic avenues for bone-related disorders like osteoporosis through targeted inhibition of this signaling cascade. [Read the Full Post]

Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development

47 | Dec 31 2023

The iterative development of a population pharmacokinetic model for ritlecitinib, integrating data from diverse clinical trials, culminated in a refined two-compartment model with direct-response non-stationary clearance, informing critical clinical decisions and shaping the drug's label across varied conditions. [Read the Full Post]

Discovery of ASP5878: Synthesis and structure-activity relationships of pyrimidine derivatives as pan-FGFRs inhibitors with improved metabolic stability and suppressed hERG channel inhibitory activity

34 | Dec 26 2023

ASP5878 (27) exhibits promising potential as a therapeutic candidate for treating bladder cancer by targeting FGFR3, boasting improved metabolic stability, minimal hERG channel inhibition, potent FGFR3 inhibition in vitro and in vivo, and favorable safety and pharmacokinetic profiles in preclinical models. [Read the Full Post]

Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats

41 | Dec 25 2023

This study on plinabulin's pharmacokinetics in rats suggests no significant differences between leukopenia and control groups, indicating its potential as a candidate for treating chemotherapy-induced leukopenia pending further human clinical trials. [Read the Full Post]

Synergistic Antibiofilm Action of Cinnamomum verum and Brazilian Green Propolis Hydroethanolic Extracts against Multidrug-Resistant Strains of Acinetobacter baumannii and Pseudomonas aeruginosa and Their Biocompatibility on Human Keratinocytes

52 | Dec 24 2023

A study evaluating Cinnamomum verum and Brazilian green propolis extracts revealed their potent antibacterial and antibiofilm properties against multidrug-resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa, showcasing biocompatibility with human cells and suggesting a promising alternative approach to combat these pathogens. [Read the Full Post]

E7050 Suppresses the Growth of Multidrug-Resistant Human Uterine Sarcoma by Inhibiting Angiogenesis via Targeting of VEGFR2-Mediated Signaling Pathways

39 | Dec 24 2023

E7050 demonstrates potent anti-tumor and anti-angiogenic effects by inhibiting VEGFR2 phosphorylation and downstream signaling pathways in endothelial cells, reducing neovessel formation in vitro and in vivo, and attenuating tumor growth and angiogenesis in a xenograft model, suggesting its promising potential as a therapeutic agent for cancer and angiogenesis-related disorders. [Read the Full Post]

NHWD-870 protects the kidney from ischemia/reperfusion injury by upregulating the PI3K/AKT signaling pathway (experimental study)

50 | Dec 23 2023

NHWD-870 exhibits substantial nephroprotective effects by attenuating renal damage through its anti-apoptotic, anti-inflammatory, and antioxidant properties, indicating potential therapeutic promise in managing renal ischemia-reperfusion injury. [Read the Full Post]

Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion

39 | Dec 18 2023

Pseudolycorine chloride (PLY), a constituent of Narcissus tazetta L. var. Chinensis Roem, demonstrates immunomodulatory effects by inhibiting myeloid-derived suppressor cells (MDSCs) and Th17 cell-mediated inflammation, making it a promising candidate for the treatment of multiple sclerosis and other autoimmune diseases. [Read the Full Post]

Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function

0 | Dec 17 2023

The study shows that small molecule tyrosine kinase inhibitors targeting Syk and BTK effectively inhibit essential platelet functions, such as adhesion, secretion, and aggregation, but exhibit differential effects on downstream signaling pathways and protein activities in platelets. [Read the Full Post]

Combined inhibition of FGFR4 and VEGFR signaling enhances efficacy in FGF19 driven hepatocellular carcinoma

21 | Dec 15 2023

The combination of Lenvatinib, a multi-kinase inhibitor, and FGFR4 inhibitor H3B-6527 demonstrates enhanced efficacy in treating FGF19-driven hepatocellular carcinoma by leveraging Lenvatinib's cell non-autonomous VEGFR activity, indicating a promising potential for clinical application. [Read the Full Post]

Lack of pharmacokinetic interaction between derazantinib and naringin in rats

29 | Dec 14 2023

The study validated a sensitive UPLC-MS/MS method for measuring derazantinib concentration in rat plasma, revealing that co-administration of derazantinib with naringin did not significantly alter its pharmacokinetic parameters, suggesting a safe concomitant use without requiring dose adjustment. [Read the Full Post]

Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor

30 | Dec 12 2023

In this study, a series of EPHA2 kinase inhibitors, including derivatives of NVP-BHG712 and triazine-based compounds, were synthesized and evaluated, revealing eight inhibitors with low-nanomolar affinities (KD <10 nM) that demonstrated promising effects in controlling human colon carcinoma, highlighting their potential as therapeutic tools in cancer research. [Read the Full Post]

Supervised screening of Tecovirimat-like compounds as potential inhibitors for the monkeypox virus E8L protein

33 | Dec 10 2023

The study utilized computational methods and machine learning-guided screening to identify five promising drugs, ABX-1431, Alflutinib, Avacopan, Caspitant, and Darapalib, which effectively engage the MPXV E8L surface binding protein with higher affinity than Tecovirimat, potentially offering new avenues for the development of personalized treatments for Monkeypox virus infections. [Read the Full Post]

The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells

44 | Dec 10 2023

The study reveals that AD80, a multikinase inhibitor, exerts potent antineoplastic effects in pancreatic cancer cells by inducing mitotic aberrations, DNA damage, autophagy, and apoptosis, providing crucial insights into potential targeted therapeutic strategies for this deadly disease. [Read the Full Post]

Single-cell RNA sequencing identifies an Il1rn+/Trem1+ macrophage subpopulation as a cellular target for mitigating the progression of thoracic aortic aneurysm and dissection

39 | Dec 08 2023

The study on thoracic aortic aneurysm and dissection (TAAD) utilizing single-cell RNA sequencing in a mouse model identified the Il1rn+/Trem1+ pro-inflammatory macrophage subpopulation as the predominant source of detrimental molecules, highlighting the potential of targeted therapy, specifically via Trem1 blockade, as a promising medical treatment for TAAD. [Read the Full Post]

Dnmt3a is downregulated by Stat5a and mediates G0/G1 arrest by suppressing the miR-17-5p/Cdkn1a axis in Jak2V617F cells

39 | Dec 06 2023

**In Jak2V617F positive classical myeloproliferative neoplasms, aberrant activation of Stat5a downregulates Dnmt3a through binding to its promoter, leading to dysregulation of the miR-17-5p/Cdkn1a axis and G0/G1 cell cycle arrest, providing a potential therapeutic target.** [Read the Full Post]

Next-Generation Sequencing-Optimal Sequencing of Therapies in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

0 | Dec 04 2023

**This research paper provides a comprehensive overview of evidence-based sequencing of therapies in relapsed/refractory chronic lymphocytic leukemia (CLL) in the era of targeted drugs, emphasizing the importance of personalized treatment strategies and highlighting promising developments, such as noncovalent BTK inhibitors, while underscoring the urgent need for solutions in the challenging subgroup of patients previously exposed to both BTK and BCL2 inhibitors.** [Read the Full Post]

Transarterial chemoembolization with or without multikinase inhibitors for patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis of randomized controlled trials

19 | Dec 04 2023

The systematic review and meta-analysis demonstrate that transarterial chemoembolization (TACE) combined with multikinase inhibitors (MKIs) significantly prolongs time to progression and improves objective response rates, but does not significantly impact overall or progression-free survival in patients with unresectable hepatocellular carcinoma, highlighting the importance of managing MKI-related toxicities in future clinical applications. [Read the Full Post]

Daprodustat: A potential game-changer in renal anemia therapy-A perspective

30 | Dec 04 2023

As of my last update in September 2021, I cannot confirm the recent FDA approval of daprodustat (DPD) for anemia due to chronic kidney disease in dialysis patients or its potential applications in non-dialysis patients and those with coexisting renal anemia and heart failure; for the latest information, please refer to official sources. [Read the Full Post]

NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response

19 | Dec 01 2023

Targeting NR4A1 with OSI-930 may offer a promising therapeutic strategy for colon adenocarcinoma patients with high immune infiltration, pending rigorous clinical validation. [Read the Full Post]

Identification of potential RapJ hits as sporulation pathway inducer candidates in Bacillus coagulans via structure-based virtual screening and molecular dynamics simulation studies

57 | Dec 01 2023

Computational analyses identified acarbose as a potential inhibitor of the RapJ enzyme, crucial for inducing the sporulation pathway in Bacillus coagulans, but experimental validation is necessary to confirm its effectiveness. [Read the Full Post]

Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice

22 | Dec 01 2023

A new study demonstrates that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation, indicating its potential as a therapeutic option for this condition. [Read the Full Post]

Neutrophil-Specific Syk Expression Is Crucial for Skin Disease in Experimental Epidermolysis Bullosa Acquisita

21 | Nov 29 2023

Syk inhibition in neutrophils emerges as a pivotal therapeutic approach for epidermolysis bullosa acquisita, preventing skin disease triggered by anti-C7 antibodies and indicating potential treatment strategies. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

107 | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

Development of Masitinib Derivatives with Enhanced Mpro Ligand Efficiency and Reduced Cytotoxicity

24 | Nov 20 2023

Using advanced molecular dynamics simulations, researchers identified masitinib's stable hydrogen bond interactions with the Mpro enzyme, pinpointing the crucial role of His163, leading to the design of effective derivatives M3 and M4 with increased inhibitory efficiency against SARS-CoV-2. [Read the Full Post]

Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells

98 | Nov 17 2023

Meticrane, a non-oncology drug originally used to treat hypertension, exhibits promising anti-cancer effects on leukemia and liver cancer cells, including synergistic interactions with epigenetic inhibitors, alterations in gene expression associated with non-cancer pathways, and considerable binding affinity to key cancer-related proteins, although it does not enhance the cytotoxicity of cytokine-induced killer cells, suggesting its potential as a novel cancer therapy warrants further investigation. [Read the Full Post]

Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2

107 | Nov 12 2023

The research reveals that tumor-associated astrocytes (TAAs) secrete lipocalin-2 (LCN2) through the STAT3 signaling pathway, promoting the progression of Sonic Hedgehog (SHH) subgroup medulloblastoma (MB) and indicating LCN2's potential as a prognostic marker and therapeutic target. [Read the Full Post]

Axin phosphorylation in condensates counteracts tankyrase-mediated degradation

37 | Nov 12 2023

The discovery of axin phosphorylation by casein kinase 1α within the tankyrase-binding site, hindering axin-tankyrase interaction and counteracting tankyrase-mediated degradation, represents a novel mechanism with implications for modulating Wnt signaling and potential cancer therapy. [Read the Full Post]

Staphylococcus aureus Infection Initiates Hypoxia-Mediated Transforming Growth Factor-β1 Upregulation to Trigger Osteomyelitis

62 | Nov 09 2023

This study reveals a novel signaling cascade involving hypoxia/HIF-1α/TGF-β1 in the pathogenesis of Staphylococcus aureus-induced osteomyelitis, highlighting its potential as a therapeutic target for the condition. [Read the Full Post]

Combined inhibition of aurora kinases and Bcl-xL induces apoptosis through select BH3-only proteins

0 | Nov 08 2023

The study demonstrates that combining small-molecule inhibitors of AURK with BH3-mimetic inhibitors targeting Bcl-xL potently induces apoptosis and may overcome resistance to AURK inhibitors in colon cancer cells. [Read the Full Post]

Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates

0 | Nov 01 2023

The study demonstrated that the combination of the MET inhibitor merestinib with the FGFR inhibitor LY2874455 showed preliminary safety and biological activity, indicating the potential of targeting MET and FGFR pathways in the treatment of relapsed/refractory acute myeloid leukemia. [Read the Full Post]

Developments and challenges of FLT3 inhibitors in acute myeloid leukemia

35 | Oct 31 2023

FLT3 mutations are common in acute myeloid leukemia (AML) and targeting FLT3 has become a crucial part of AML treatment, although resistance to FLT3 inhibitors remains a challenge that is being addressed through the development of novel agents and multitarget strategies. [Read the Full Post]

CX3CL1 in the red bone marrow promotes renal cell carcinoma to metastasize to the spine by involving the Src-related pathway

48 | Oct 30 2023

CX3CL1 promotes migration and invasion of renal cell carcinoma (RCC) cells, potentially facilitating RCC metastasis to the spine, through activation of the Src/FAK signaling pathway. [Read the Full Post]

Kaempferol suppresses glioma progression and synergistically enhances the antitumor activity of gefitinib by inhibiting the EGFR/SRC/STAT3 signaling pathway

64 | Oct 20 2023

The study found that kaempferol (Kae) inhibits glioma cell proliferation, promotes apoptosis, and inhibits migration and invasion, potentially through targeting EGFR/SRC/STAT3 signaling, and synergizes with gefitinib (Gef) to enhance antitumor effects, suggesting its potential as a candidate drug or chemosensitizer in glioma therapy. [Read the Full Post]

Investigation of Fenebrutinib Metabolism and Bioactivation Using MS3 Methodology in Ion Trap LC/MS

27 | Oct 17 2023

Fenebrutinib, an orally available Bruton tyrosine kinase inhibitor, has been characterized through in silico and in vitro studies, elucidating its metabolites and reactive intermediates, which can aid in understanding its adverse effects and facilitate the development of safer drugs. [Read the Full Post]

Inhibition of ErbB3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival

26 | Oct 16 2023

The study identified erbB3, calmodulin, PIM kinases, and Src family members as potential therapeutic targets in MPNSTs and demonstrated that combinatorial therapies targeting these pathways are more effective in reducing proliferation and survival. [Read the Full Post]

A phase 1b study of the allosteric extracellular FGFR2 inhibitor alofanib in patients with pretreated advanced gastric cancer

29 | Oct 14 2023

Alofanib, a small-molecule allosteric extracellular FGFR2 inhibitor, showed acceptable tolerability and preliminary signs of clinical activity in heavily pretreated patients with advanced gastric cancer, with a recommended phase 2 dose of 350 mg/m2 administered 5 days on and 2 days off. [Read the Full Post]

PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis

63 | Oct 14 2023

Proline-rich tyrosine kinase 2B (PTK2B) plays a role in the pathogenesis of ulcerative colitis (UC) by promoting neutrophil migration and inhibiting mucosal inflammation, making it a potential therapeutic target for UC treatment. [Read the Full Post]

Olverembatinib Treatment in Pediatric Patients With Relapsed Philadelphia-Chromosome-Positive Acute Lymphoblastic Leukemia

68 | Oct 13 2023

In this study, olverembatinib demonstrated both safety and efficacy in children with relapsed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), including some achieving complete remission as a single agent. [Read the Full Post]

Inhibiting HIF-1 signaling alleviates HTRA1-induced RPE senescence in retinal degeneration

28 | Oct 12 2023

Elevated levels of HTRA1 in age-related macular degeneration (AMD) contribute to retinal pigment epithelium (RPE) senescence by damaging mitochondrial function and activating HIF-1 signaling, suggesting the inhibition of HIF-1 signaling as a potential therapeutic strategy for AMD. [Read the Full Post]

Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study

70 | Oct 09 2023

This study aimed to identify new ligands for the platelet-derived growth factor receptor (PDGFR) through screening of thousands of compounds, resulting in the selection of potential drugs and natural compounds with high affinity, providing valuable insights for the development of more effective treatments for PDGFR-related diseases. [Read the Full Post]

Cell surface ATP synthase-released H+ and ATP play key roles in cocoa butter intake-mediated regulation of gut immunity through releases of cytokines in rat

41 | Oct 06 2023

Cocoa butter intake regulates gut immunity by increasing lymph flow, cell density, and the release of IL-1β, IL-6, and IL-10 in mesenteric lymph, with the involvement of macrophages, cell surface ATP synthase, and pH-dependent cytokine release. [Read the Full Post]

ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming

0 | Oct 02 2023

This study reveals that targeting FGFR1 and mTOR in combination can overcome drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) by inhibiting ATF4-mediated amino acid metabolic reprogramming. [Read the Full Post]

Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

0 | Oct 02 2023

This review discusses the concept of relapsed chronic lymphocytic leukemia (CLL), available treatment options, and emerging therapies, emphasizing the need for individualized therapy selection and the ongoing research in this field. [Read the Full Post]

Safety and tolerability of oral vorolanib for neovascular (wet) age-related macular degeneration: a phase I, open-label study

31 | Oct 01 2023

The study demonstrated that oral vorolanib improved visual outcomes in participants with neovascular age-related macular degeneration (nAMD) while maintaining a manageable safety profile. [Read the Full Post]

Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

25 | Sep 30 2023

This review examines the recent advancements in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), including targeted therapies, chimeric antigen receptor (CAR) T cell therapy, and the role of measurable residual disease (MRD) assessment, providing insights into therapeutic options and considerations for individualized treatment selection. [Read the Full Post]

ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming

20 | Sep 29 2023

This study demonstrates that targeting FGFR1 in human T-cell acute lymphoblastic leukemia (T-ALL) is a potential therapeutic strategy, but the development of resistance to FGFR1 inhibitors is mediated by ATF4-mediated amino acid metabolic reprogramming, which can be overcome by synergistically inhibiting FGFR1 and mTOR. [Read the Full Post]

Diazoxide improves muscle function in association with improved dyslipidemia and decreased muscle oxidative stress in streptozotocin-induced diabetic rats

30 | Sep 27 2023

Diazoxide administration in diabetic rats improves muscle strength development, reduces fatigue, lowers cholesterol and triglyceride levels, and improves oxidative stress parameters, suggesting its potential as a therapeutic intervention for diabetes-related complications. [Read the Full Post]

Precious Gene: The Application of RET-Altered Inhibitors

115 | Sep 23 2023

The novel RET-specific inhibitors selpercatinib and pralsetinib, along with ongoing clinical trials of TPX-0046 and zetletinib, demonstrate promising efficacy and safety in the treatment of RET-altered cancers, addressing the limitations of previous multikinase inhibitors. [Read the Full Post]

Discovery of the allosteric inhibitor from actinomyces metabolites to target EGFRCSTMLR mutant protein: molecular modeling and free energy approach

20 | Sep 20 2023

The study identified compound C_42 as a potential drug candidate with strong binding affinity, favorable structural characteristics, and promising potential as an EGFR inhibitor for cancer treatment. [Read the Full Post]

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors

65 | Sep 19 2023

Selective TYK2 inhibitors, such as deucravacitinib and ropsacitinib, offer a promising approach for treating inflammatory and autoimmune diseases with improved efficacy and safety profiles compared to broad JAK inhibitors. [Read the Full Post]

Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis

36 | Sep 18 2023

The systematic review and network meta-analysis found that hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) did not significantly differ from erythropoiesis-stimulating agents (ESAs) in terms of overall adverse events and serious adverse events, but differences were observed in gastrointestinal disorder, hypertension, vascular-access complications, and hemoglobin response. [Read the Full Post]

Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase

44 | Sep 18 2023

[18F]PTBTK3, a PET radiotracer based on a selective BTK inhibitor, demonstrates BTK-dependent tumor uptake in BTK-positive tumors, showing promise for the diagnosis and development of BTK-targeted therapies. [Read the Full Post]

Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response

71 | Sep 18 2023

Remibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, effectively inhibits the activation of basophils and mast cells induced by serum from chronic urticaria patients, regardless of their responsiveness to omalizumab treatment. [Read the Full Post]

Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors

76 | Sep 18 2023

Deucravacitinib, an allosteric tyrosine kinase 2 inhibitor, has been approved as a first-in-class treatment for moderate-to-severe plaque psoriasis and shows improved safety compared to orthosteric Janus kinase inhibitors. [Read the Full Post]

Evaluation of Drug-Drug Interaction Potential of Enarodustat (JTZ-951) Using a Cytochrome P450 Probe Cocktail

67 | Sep 17 2023

Enarodustat, administered at doses of 25 mg and 50 mg, showed minimal to no significant drug interactions with cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6, and 3A4 in a phase 1 multiple-ascending-dose study, with changes in geometric mean ratios generally being less than 2-fold. [Read the Full Post]

BRAF v600E-mutant cancers treated with vemurafenib alone or in combination with everolimus, sorafenib, or crizotinib or with paclitaxel and carboplatin (VEM-PLUS) study

67 | Sep 16 2023

The VEM-PLUS study found that combining vemurafenib with cytotoxic chemotherapy or RAF- or mTOR-targeting agents did not significantly improve overall survival or progression-free survival compared to vemurafenib monotherapy in patients with solid tumors harboring BRAF V600E mutations. [Read the Full Post]

Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors

54 | Sep 09 2023

BI-4020, a noncovalent, wild-type EGFR sparing, macrocyclic TKI, demonstrates potent inhibition of EGFR variants including T790M and C797S, and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. [Read the Full Post]

Two is company, is three a crowd? Triplet therapy, novel molecular targets, and updates on the management of advanced renal cell carcinoma

69 | Sep 06 2023

Recent advances in the management of advanced renal cell carcinoma include the favorability of nivolumab plus cabozantinib in combination therapy, promising results from triplet therapy and HIF-2α inhibitors, investigation of metabolic pathway inhibitors and biomarkers, and the ongoing evaluation of cytoreductive nephrectomy in the context of combination therapy. [Read the Full Post]

Deuterium in drug discovery: progress, opportunities and challenges

114 | Sep 05 2023

Deuteration, the substitution of a hydrogen atom with its heavy isotope deuterium, has emerged as a promising strategy in drug discovery and development, offering the potential to enhance drug efficacy and safety through improved pharmacokinetic and toxicity profiles. [Read the Full Post]

Clinical Utility of Deucravacitinib for the Management of Moderate to Severe Plaque Psoriasis

82 | Sep 05 2023

Deucravacitinib, a first-in-class TYK2 small molecule inhibitor, shows significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe psoriasis based on a systematic review and meta-analysis of randomized controlled trials. [Read the Full Post]

Evaluation of the Cytochrome P450 3A and P-glycoprotein Drug-Drug Interaction Potential of Futibatinib

23 | Sep 01 2023

Futibatinib, an FGFR1-4 inhibitor, should not be concomitantly used with dual P-gp and strong CYP3A inhibitors/inducers but can be administered alongside other drugs metabolized by CYP3A, as demonstrated in phase I studies. [Read the Full Post]

Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial

60 | Aug 28 2023

The phase IIb study showed that brepocitinib at doses of 30 mg and 60 mg once daily (QD) was more effective than placebo in reducing symptoms of psoriatic arthritis (PsA) and demonstrated a favorable safety profile throughout the 52-week study. [Read the Full Post]

BTK Inhibitors in the Frontline Management of Waldenström Macroglobulinemia

55 | Aug 27 2023

BTK inhibitors, such as ibrutinib and zanubrutinib, have shown promising results in both treatment-naïve and relapsed/refractory Waldenström macroglobulinemia (WM) patients, with improved response rates and prolonged progression-free survival. [Read the Full Post]

How We Manage Patients with Indolent B-Cell Malignancies on Bruton's Tyrosine Kinase Inhibitors: Practical Considerations for Nurses and Pharmacists

0 | Aug 27 2023

This paper aims to provide Canadian nurses and pharmacists with a comprehensive reference on dosing, co-administration, and adverse event management strategies for patients with indolent B-cell NHL or CLL undergoing treatment with BTK inhibitors, addressing the evolving treatment landscape and unique safety profiles of these agents. [Read the Full Post]

Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines

68 | Aug 26 2023

Zanubrutinib, a small molecule Bruton's tyrosine kinase (BTK) inhibitor, has shown potential as an inhibitor of the HER2 signaling pathway and a candidate for repurposing in HER2-positive breast cancer. [Read the Full Post]

Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors

74 | Aug 26 2023

AZD3229 is a potent and selective small-molecule inhibitor with the potential to be a best-in-class treatment for a broad range of primary and imatinib-resistant secondary mutations in gastrointestinal stromal tumor (GIST). [Read the Full Post]

Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary

37 | Aug 25 2023

The summary discusses a clinical study that found abrocitinib to be more effective than dupilumab in quickly improving the signs and symptoms of moderate to severe atopic dermatitis (AD) in individuals who did not respond to prescribed topical medications. [Read the Full Post]

Efficacy and safety of abrocitinib for moderate-to-severe atopic dermatitis in adolescents and adults: Meta-analysis

109 | Aug 25 2023

This meta-analysis suggests that abrocitinib is both safe and effective in treating moderate-to-severe atopic dermatitis in adolescents and adults, with the 200 mg dose showing a greater efficacy compared to the 100 mg dose. [Read the Full Post]

SEOM-GEIS clinical guideline for gastrointestinal stromal tumors (2022)

73 | Aug 24 2023

The Spanish Society of Medical Oncology (SEOM) and the Spanish Sarcoma Research Group (GEIS) recommend a multidisciplinary approach and centralized management in reference centers for the diagnosis and treatment of gastrointestinal stromal tumor (GIST) patients. [Read the Full Post]

Ripretinib in advanced gastrointestinal stromal tumors: an overview of current evidence and drug approval

39 | Aug 24 2023

Ripretinib, a switch-control tyrosine kinase inhibitor, has shown promise in targeting both primary and secondary KIT and PDGFRα resistance mutations, making it a valuable therapeutic option in the management of advanced gastrointestinal stromal tumors (GISTs) that have developed resistance to imatinib and other treatments. [Read the Full Post]

Anti-tumor efficacy of the novel KIT inhibitor IDRX-42 (formerly M4205) in patient- and cell line-derived xenograft models of gastrointestinal stromal tumor (GIST)

28 | Aug 11 2023

The study found that IDRX-42, a novel selective KIT inhibitor, exhibited significant antitumor activity by inducing tumor volume shrinkage, reducing mitotic activity, and causing characteristic myxoid degeneration in GIST xenograft models with specific KIT mutations. [Read the Full Post]

Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib

46 | Aug 11 2023

This study proposes the use of AI-designed gamma-tocotrienol (AIGT) as a potential therapeutic option for chronic myeloid leukemia (CML) by targeting the BCR-ABL1 fusion protein, exhibiting promising efficacy and potential hepatoprotective properties compared to existing medications. [Read the Full Post]

The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With At Least 2 Tyrosine Kinase Inhibitors

80 | Aug 11 2023

Asciminib, an allosteric high-affinity tyrosine kinase inhibitor, received marketing authorization from the European Commission for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase after evaluating its clinical efficacy and safety in the phase III ASCEMBL study. [Read the Full Post]

FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling

16 | Aug 10 2023

The study revealed that the combination therapy targeting FGFR4 and EZH2 inhibitors synergistically induced apoptosis and inhibited hepatocellular carcinoma (HCC) development, highlighting its potential as a promising therapeutic strategy for HCC treatment. [Read the Full Post]

Integration of Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy into Model-Informed Dose Selection in Oncology First-in-Human Study: A Case of Roblitinib (FGF401)

66 | Aug 10 2023

The paper presents a comprehensive modeling and simulation framework that integrates pharmacometrics and statistical methods to inform dose selection of FGF401, a selective FGFR4 inhibitor, in oncology early clinical development, utilizing pharmacokinetic, pharmacodynamic, safety, and efficacy data. [Read the Full Post]

A phase II trial of GSK2256098 and trametinib in patients with advanced pancreatic ductal adenocarcinoma

68 | Aug 08 2023

The combination of GSK2256098 and trametinib did not show significant clinical benefit in advanced pancreatic ductal adenocarcinoma (PDAC) patients, with short median progression-free survival and overall survival observed in the study. [Read the Full Post]

A phase Ib/II study of BLU-554, a fibroblast growth factor receptor 4 inhibitor in combination with CS1001, an anti-PD-L1, in patients with locally advanced or metastatic hepatocellular carcinoma

64 | Aug 07 2023

The preliminary trial results indicate that combining BLU-554 and CS1001 is a safe and effective treatment option for patients with locally advanced or metastatic hepatocellular carcinoma (HCC), with a 50% objective response rate and 100% disease control rate observed. [Read the Full Post]

FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC

88 | Aug 07 2023

The study revealed that elevated expression of E74-like factor 4 (ELF4) in colorectal cancer is associated with increased metastasis and poor prognosis, and targeting the ELF4-related positive feedback circuit may offer a novel therapeutic approach. [Read the Full Post]

Metabolic study of hypoxia-inducible factor stabilizers BAY 87-2243, MK-8617, and PT-2385 in equine liver microsomes for doping control

49 | Aug 03 2023

This study identified multiple metabolites, including hydroxylated and glucuronic acid conjugated forms, for the hypoxia-inducible factor-prolyl hydroxylase inhibitor compounds BAY 87-2243, MK-8617, and PT-2385 in equine liver microsomes, shedding light on their metabolic pathways and potential misuse as performance enhancers. [Read the Full Post]

VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis

62 | Aug 03 2023

This study demonstrates the potential of VH298-loaded extracellular vesicles (EVs) and GelMA hydrogel as a promising therapeutic strategy for diabetic wound treatment, promoting angiogenesis and enhancing wound healing. [Read the Full Post]

Liver Fibrosis, Fat, and Iron Evaluation with MRI and Fibrosis and Fat Evaluation with US: A Practical Guide for Radiologists

68 | Aug 02 2023

This review provides a practical guide for radiologists on the interpretation of liver disease using MRI and US, focusing on quantitative imaging biomarkers such as liver fibrosis, fat, and iron, and covering technical requirements, measurement techniques, case interpretation guidelines, and potential pitfalls. [Read the Full Post]

Successful Treatment and Retreatment With Erdafitinib for a Patient With FGFR3-TACC3 Fusion Squamous NSCLC: A Case Report

119 | Aug 01 2023

This case report demonstrates the potential efficacy of erdafitinib, an FGFR inhibitor, in achieving disease control and radiographic response in a patient with FGFR3-TACC3 fusion squamous NSCLC, suggesting the need for further investigation and expanding therapeutic options. [Read the Full Post]

Current scenario of pyrazole hybrids with in vivo therapeutic potential against cancers

93 | Aug 01 2023

This review provides a comprehensive overview of the potential of pyrazole hybrids as anticancer agents, summarizing their mechanisms of action, toxicity, and pharmacokinetics, with the aim of facilitating the rational exploitation and development of more effective candidates for cancer therapy. [Read the Full Post]

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence

35 | Jul 31 2023

This literature review examines the risks and safety of combining radiotherapy with anti-HER2 therapies in breast cancer, suggesting that monoclonal antibodies and checkpoint inhibitors can be safely combined with radiation, while caution is warranted for tyrosine kinase inhibitors and antibody-drug conjugates due to limited evidence. [Read the Full Post]

HIF2 Inactivation and Tumor Suppression with a Tumor-Directed RNA-Silencing Drug in Mice and Humans

16 | Jul 30 2023

This study demonstrated the successful inhibition of HIF2α and tumor suppression using a systemic, tumor-directed, RNA-silencing drug (siHIF2), providing a proof-of-principle for targeted RNA-based therapeutics in clear cell renal cell carcinomas (ccRCC). [Read the Full Post]

Specific HIF-2α (Hypoxia-Inducible Factor-2) Inhibitor PT2385 Mitigates Placental Dysfunction In Vitro and in a Rat Model of Preeclampsia (RUPP)

33 | Jul 30 2023

The study demonstrates that PT2385, an oral specific HIF-2α inhibitor, shows promise in treating severe placental dysfunction associated with preeclampsia by enhancing cytotrophoblast differentiation, normalizing angiogenic factor secretion, and preventing the onset of maternal symptoms in an animal model. [Read the Full Post]

A narrative review from gut to lungs: non-small cell lung cancer and the gastrointestinal microbiome

96 | Jul 24 2023

The gut microbiome plays a crucial role in modulating the immune response and therapeutic outcomes in lung cancer, highlighting the potential for microbiome-based interventions to improve treatment efficacy. [Read the Full Post]

A case of nocardiosis in a patient with ulcerative colitis on chronic corticosteroids, infliximab, and upadacitinib

99 | Jul 21 2023

Immunosuppressed patients, particularly those with ulcerative colitis, are at an increased risk of unmasking obscure infections, necessitating early detection and treatment to mitigate the associated morbidity and mortality. [Read the Full Post]

The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis

34 | Jul 21 2023

Upadacitinib demonstrated higher therapeutic efficacy in reducing skin rashes in the lower limbs compared to the trunk and head and neck in patients with moderate-to-severe atopic dermatitis. [Read the Full Post]

Treatment satisfaction with molidustat in CKD-related anemia in non-dialysis patients: a post-hoc analysis of two clinical trials

33 | Jul 20 2023

The post-hoc analysis suggests that molidustat may offer improved treatment satisfaction and convenience compared to darbepoetin alfa for patients with non-dialysis chronic kidney disease and renal anemia. [Read the Full Post]

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease

25 | Jul 20 2023

In conclusion, roxadustat demonstrated the highest efficacy in increasing hemoglobin levels but was associated with an increased risk of hypertension and thrombosis, while molidustat and ESAs may be preferable options for patients at risk of hypertension and thrombosis. [Read the Full Post]

How We Manage Patients with Indolent B-Cell Malignancies on Bruton's Tyrosine Kinase Inhibitors: Practical Considerations for Nurses and Pharmacists

35 | Jul 19 2023

This paper provides Canadian nurses and pharmacists with a comprehensive reference guide on dosing, co-administration, and adverse event management strategies for patients with indolent B-cell NHL or CLL being treated with Bruton's tyrosine kinase (BTK) inhibitors. [Read the Full Post]

BET inhibition targets ABC-DLBCL constitutive B-cell receptor signaling through PAX5

25 | Jul 19 2023

The study demonstrates that combining the BET inhibitor AZD5153 with the Bruton tyrosine kinase inhibitor acalabrutinib enhances efficacy in ABC-DLBCL by targeting PAX5 and BCR signaling pathways, offering potential for improved treatment outcomes in relapsed or refractory patients. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

0 | Jul 15 2023

Myelofibrosis, a hematologic malignancy characterized by splenomegaly, is primarily treated with JAK inhibitors, although spleen size reduction is not consistent, and new pharmacotherapies and combination treatments are being explored to improve outcomes. [Read the Full Post]

Comprehensive profiling of clinical JAK inhibitors in myeloproliferative neoplasms

86 | Jul 15 2023

The comprehensive profiling of four JAK2 inhibitors revealed their distinct clinical profiles, including differential effects on JAK-STAT signaling, inflammatory response, erythroid colony formation, leukemic engraftment, and iron regulation, providing valuable insights for personalized therapy in myeloproliferative neoplasm patients. [Read the Full Post]

Formaldehyde exacerbates asthma in mice through the potentiation of HIF-1α-mediated pro-inflammatory responses in pulmonary macrophages

30 | Jul 08 2023

The study revealed that formaldehyde exposure exacerbates asthma by enhancing HIF-1α-mediated inflammatory responses in macrophages, indicating the potential universal role of formaldehyde-induced macrophage metabolic and functional alterations in inflammatory or allergic diseases. [Read the Full Post]

Exploring Synthetic Strategies for 1H-Indazoles and Their N-Oxides: Electrochemical Synthesis of 1H-Indazole N-Oxides and Their Divergent C-H Functionalizations

78 | Jul 08 2023

The research study describes a versatile electrochemical strategy for the selective synthesis of 1H-indazole N-oxides and their subsequent C-H functionalization, demonstrating its potential for the synthesis of diverse pharmaceutical molecules. [Read the Full Post]

Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS

43 | Jul 06 2023

RAS proteins, including KRAS, HRAS, and NRAS, function as GTPases and play crucial roles in cell signaling pathways involved in growth, division, and survival, with RAS mutations being common in various cancers, particularly KRAS mutations in lung, colorectal, and pancreatic cancers. [Read the Full Post]

Itacitinib Population Pharmacokinetics and Exposure-Response in Patients With Acute Graft-Versus-Host Disease

50 | Jul 01 2023

This article presents a population pharmacokinetic analysis and exposure-response assessment of itacitinib for the treatment of acute graft-versus-host disease, revealing significant predictors of treatment response and recommending dose reductions when co-administered with strong CYP3A inhibitors. [Read the Full Post]

Erlotinib-Loaded Dendrimer Nanocomposites as a Targeted Lung Cancer Chemotherapy

37 | Jun 28 2023

The study found that the cationic G4 PAMAM dendrimer formulation of erlotinib showed superior antiproliferative activity against A549 lung cells compared to neutral G5 dendrimers and erlotinib alone, suggesting its potential as a targeted and sustained-release carrier for lung cancer treatment. [Read the Full Post]

Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing

87 | Jun 28 2023

This case study showcases the efficacy of ex vivo drug testing using patient-derived tumor organoids as a precision medicine approach, leading to significant clinical improvement and prolonged stable disease in a patient with platinum-resistant, advanced low-grade serous ovarian cancer. [Read the Full Post]

Advances in clinical studies of FLT3 inhibitors in acute myeloid leukemia

37 | Jun 26 2023

This comprehensive review article examines the current status of FLT3 inhibitors in clinical research for acute myeloid leukemia (AML) patients and explores treatment strategies, including combination therapies, to overcome drug resistance and improve patient outcomes. [Read the Full Post]

Structural insights into the potency and selectivity of covalent pan-FGFR inhibitors

76 | Jun 24 2023

This study investigates the potency, selectivity, and ability to overcome gatekeeper mutations of covalent pan-FGFR inhibitors, providing valuable insights for the development of next-generation inhibitors with improved properties. [Read the Full Post]

Molecular Docking, Molecular Dynamics Simulations, and Free Energy Calculation Insights into the Binding Mechanism between VS-4718 and Focal Adhesion Kinase

111 | Jun 21 2023

This research work elucidates the binding mechanism between VS-4718 and focal adhesion kinase (FAK), providing valuable insights for optimizing the design of FAK inhibitors in cancer therapy. [Read the Full Post]

An intuitionistic approach for the predictability of anti-angiogenic inhibitors in cancer diagnosis

84 | Jun 21 2023

This research employs the PROMETHEE-II decision-making algorithm and fuzzy models to rank and determine the most efficacious anti-angiogenesis inhibitors for cancer treatment based on the evaluation of growth factors and predefined criteria. [Read the Full Post]

FOXK1 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway

101 | Jun 20 2023

Interference with FOXK1 in nasopharyngeal carcinoma cells through the JAK/STAT3 pathway regulates EMT, enhances radiosensitivity, and inhibits tumor progression [Read the Full Post]

JAK inhibitors for rheumatoid arthritis

0 | Jun 20 2023

JAK inhibitors have shown promise in treating rheumatoid arthritis by selectively modulating immune and inflammatory pathways, although their in vivo selectivity and long-term safety profile still require further investigation. [Read the Full Post]

Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response

49 | Jun 20 2023

The study revealed that transfection of specific microRNAs enhanced the sensitivity of malignant pleural mesothelioma cells to chemotherapy and a FAK inhibitor, while also demonstrating that YM155-resistant cells showed increased exosome secretion and upregulation of drug transporter genes ABCA6 and ABCA10, which correlated with poor sensitivity to YM155. [Read the Full Post]

Constitutive JAK/STAT signaling is the primary mechanism of resistance to JAKi in TYK2-rearranged acute lymphoblastic leukemia

107 | Jun 19 2023

The study demonstrates that sustained treatment with the JAK/TYK2 inhibitor cerdulatinib leads to JAK1 overexpression and enhanced JAK/STAT signaling in TYK2-rearranged ALL cells, but withdrawal of the drug reverses these effects, while histone deacetylase inhibitor (HDACi) therapies show efficacy against cerdulatinib-resistant cells, offering a potential alternative treatment approach for TYK2-rearranged B-ALL patients who have developed resistance to JAKi. [Read the Full Post]

Health Status, Quality of Life, Psychosocial Well-being, and Wearables Data of Patients With Active Ulcerative Colitis Receiving Filgotinib Therapy (FilgoColitis Study): Protocol for a Real-world Observational Study

66 | Jun 18 2023

The FilgoColitis study is a prospective observational study evaluating the long-term effectiveness of filgotinib in patients with active ulcerative colitis, focusing on patient-reported outcomes and incorporating the use of innovative wearables to collect physical activity data. [Read the Full Post]

Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

35 | Jun 18 2023

This interventional clinical trial aims to compare the effectiveness of filgotinib monotherapy to tocilizumab monotherapy in rheumatoid arthritis patients with an inadequate response to methotrexate, utilizing clinical disease activity indices, musculoskeletal ultrasound, and serum biomarkers as evaluation parameters. [Read the Full Post]

A Non-Canonical Role for the Glycosyltransferase Enzyme UGT2B17 as a Novel Constituent of the B Cell Receptor Signalosome

45 | Jun 18 2023

Elevated expression of glycosyltransferase UGT2B17 in chronic lymphocytic leukemia (CLL) is associated with poor survival, enhanced BCR pathway signaling, and increased phosphorylation of Bruton tyrosine kinase (BTK), highlighting its potential as an oncogenic factor and therapeutic target. [Read the Full Post]

From preclinical efficacy to 2022 updated CROWN trial, lorlatinib is the preferred 1st-line treatment of advanced ALK+ NSCLC

118 | Jun 14 2023

The data from the CROWN trial, including the sustained and durable responses, favorable 3-year progression-free survival rates, and manageable CNS adverse events, strongly support lorlatinib as the preferred treatment for advanced ALK+ NSCLC. [Read the Full Post]

GEF-H1 Transduces FcεRI Signaling in Mast Cells to Activate RhoA and Focal Adhesion Formation during Exocytosis

84 | Jun 13 2023

The study found that GEF-H1 acts as a signal transducer, activating RhoA and promoting mast cell spreading and exocytosis, thus playing a crucial role in antigen-stimulated mast cell activation. [Read the Full Post]

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial

28 | Jun 13 2023

The combination of entospletinib and decitabine showed limited efficacy with low complete remission rates and short overall survival in older patients with acute myeloid leukemia (AML) and specific genetic mutations or karyotype abnormalities. [Read the Full Post]

Dimethyloxalylglycine Attenuates Steroid-Associated Endothelial Progenitor Cell Impairment and Osteonecrosis of the Femoral Head by Regulating the HIF-1α Signaling Pathway

34 | Jun 11 2023

Targeting hypoxia-inducible factor-1α (HIF-1α) in endothelial progenitor cells (EPCs) may offer a novel therapeutic approach for the treatment of steroid-associated osteonecrosis of the femoral head (SONFH) by alleviating glucocorticoid-induced endothelial impairment, promoting angiogenesis and osteogenesis, and enhancing the homing of EPCs to the injured endothelium. [Read the Full Post]

Systemic treatment in patients with Child-Pugh B liver dysfunction and advanced hepatocellular carcinoma

86 | Jun 07 2023

Hepatocellular carcinoma (HCC) is a major cause of death among patients with liver cirrhosis, and the limited efficacy of available therapies in patients with moderate liver dysfunction highlights the need for improved treatment algorithms and novel therapies specifically designed for this patient population. [Read the Full Post]

NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors

116 | Jun 03 2023

This study highlights the need for cautious evaluation and dosage optimization of inhibitors targeting respiratory complex I in cancer treatment. [Read the Full Post]

Discovery of Potent and Wild-Type-Sparing Fourth-Generation EGFR Inhibitors for Treatment of Osimertinib-Resistance NSCLC

98 | Jun 02 2023

The development of Osimertinib derivatives as fourth-generation inhibitors for the treatment of Osimertinib-resistant NSCLC, particularly the top candidate D51, shows promising selectivity and antitumor activity with favorable in vivo druggability. [Read the Full Post]

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase

60 | May 22 2023

The study investigated the molecular mechanism of action of Commiphora myrrha (CM)-induced insulin secretion and found that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling, which is completely dependent on protein kinase activation, particularly the phosphorylation and activation of PKCζ and ERK1/2. [Read the Full Post]

Tyrosine Kinase Inhibitors Target B Lymphocytes

142 | May 20 2023

Protein kinase inhibitors previously used to treat ALK-positive lung cancer cells have shown potential in targeting LTK-positive B cells, providing new treatment options for autoimmune disorders and blood cancers. [Read the Full Post]

Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates

91 | May 19 2023

The study provides preliminary evidence that the combination therapy with MET and FGFR inhibitors is a safe and biologically active treatment option for patients with relapsed/refractory acute myeloid leukemia. [Read the Full Post]

Structural, spectroscopic, luminescence sensing and TD-DFT theoretical studies of a CuP2N-type complex

85 | May 18 2023

The passage describes a heteroleptic cuprous complex with a CuP2N coordination triangle, which exhibits UV-Vis absorption due to LLCT characteristic excited states and luminescence light-up sensing for pyridine in a paper-based film. [Read the Full Post]

Low gamma-butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach

38 | May 17 2023

This study found that low BBOX1 expression in clear cell renal cell carcinoma (RCC) patients is associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils, and identified potential drugs, including midostaurin, that can inhibit RCC cells with low BBOX1 expression. [Read the Full Post]

Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models

104 | May 16 2023

UBX-382 is a potent and orally available PROTAC that effectively targets both wild-type and mutant BTK proteins to inactivate B-cell receptor signaling, leading to complete tumor regression in murine xenograft models within 2 weeks of oral dosing. [Read the Full Post]

A phase I/II study of epertinib plus trastuzumab with or without chemotherapy in patients with HER2-positive metastatic breast cancer

103 | May 15 2023

This study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of daily oral epertinib combined with trastuzumab, vinorelbine, or capecitabine in patients with pre-treated HER2-positive metastatic breast cancer, with promising results. [Read the Full Post]

Comparative effectiveness of mobocertinib and standard of care in patients with NSCLC with EGFR exon 20 insertion mutations: An indirect comparison

53 | May 14 2023

This study compared the effectiveness of mobocertinib, a novel EGFR tyrosine kinase inhibitor, with real-world treatments in platinum-pretreated patients with advanced EGFR ex20ins-mutant NSCLC, and found that mobocertinib provided substantially improved outcomes. [Read the Full Post]

Molecular Design of 68Ga- and 89Zr-Labeled Anticalin Radioligands for PET-Imaging of PSMA-Positive Tumors

62 | May 05 2023

The study demonstrates the potential of Anticalin proteins as radioligands for PET-imaging of xenograft tumors in mice, with the use of PASylation technology to tailor their plasma half-life and the cyclic radiochelator FsC being superior to Dfo for 89Zr-ImmunoPET-imaging. [Read the Full Post]

Apatinib combined with SOX regimen for conversion therapy in advanced gastric cancer patients: a retrospective cohort study

76 | May 02 2023

The study shows that conversion chemotherapy followed by surgery and apatinib-targeted therapy combined with SOX chemotherapy may be beneficial for patients with advanced gastric cancer. [Read the Full Post]

JAK inhibitors for rheumatoid arthritis

89 | Apr 29 2023

JAK inhibitors represent a promising class of drugs for the treatment of rheumatoid arthritis, with varying degrees of selectivity for different JAK isoforms, and precision medicine approaches may enhance their effectiveness in the future. [Read the Full Post]

Omicron-induced interferon signalling prevents influenza A H1N1 and H5N1 virus infection

93 | Apr 09 2023

Recent research shows that Omicron but not Delta induces a strong interferon response in primary human cells, protects cells from super-infection with influenza A viruses, and the response is mediated via MDA5 recognition of double-stranded RNA and involves the production of biologically active type I (α/β) and III (λ) interferons. [Read the Full Post]

Excellent Repigmentation of Generalized Vitiligo with Oral Baricitinib Combined with NB-UVB Phototherapy

67 | Apr 09 2023

Oral baricitinib combined with NB-UVB phototherapy has shown to be a successful treatment option for refractory vitiligo by blocking the JAK-STAT pathway and stimulating melanocyte production. [Read the Full Post]

Integrated profiling uncovers prognostic, immunological, and pharmacogenomic features of ferroptosis in triple-negative breast cancer

34 | Apr 08 2023

The study explores the role of ferroptosis in TNBC, identifying different patterns of ferroptosis associated with prognostic and immunological traits, proposing a ferroptosis-relevant scoring system, and predicting small-molecule agents for high-risk patients. [Read the Full Post]

Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus

177 | Apr 05 2023

This research demonstrates that mutations in the K-D-K-E methyltransferase motif restrict the cell-to-cell spread of Newcastle disease virus via tunnelling nanotubes. [Read the Full Post]

Successful Treatment with Crizotinib to Overcome Drug Resistance Possibly Due to Mesenchymal-epithelial Transition Amplification in a Lung Cancer Patient with the Echinoderm Microtubule-associated Protein-like 4-anaplastic Lymphoma Kinase Fusion Gene

43 | Apr 04 2023

This case report highlights the potential effectiveness of crizotinib, a MET inhibitor, in ALK-positive lung cancer patients with MET amplification who have developed resistance to ALK-TKIs. [Read the Full Post]

Monitoring paxillin in astrocytes reveals the significance of the adhesion GPCR VLGR1/ADGRV1 for focal adhesion assembly

97 | Apr 04 2023

VLGR1 is a vital component of focal adhesions and regulates cell migration by controlling focal adhesion turnover during their assembly, and its dysfunctions may contribute to the pathogenesis of Usher syndrome, epilepsy, and other related diseases. [Read the Full Post]

A Novel Quantum Dots-Based Fluorescent Sensor for Determination of the Anticancer Dacomitinib: Application to Dosage Forms

53 | Apr 01 2023

The study proposes a novel spectrofluorimetric method for determining the concentration of dacomitinib using newly synthesized nitrogen-doped carbon quantum dots as fluorescent probes, which exhibit native fluorescence and are selectively quenched by increasing concentrations of dacomitinib, offering a simple, efficient, and eco-friendly means of determining the concentration of dacomitinib. [Read the Full Post]

An evaluation of fedratinib for adult patients with newly diagnosed and previously treated myelofibrosis

111 | Apr 01 2023

Fedratinib is a selective JAK2 inhibitor that has been approved by the FDA for the treatment of intermediate-2 or high-risk primary or secondary MF, providing a second-line treatment option for patients who failed or discontinued ruxolitinib, but new combinations with other targeted therapies are needed to improve management of the disease. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

129 | Apr 01 2023

Myelofibrosis is a hematologic malignancy characterized by splenomegaly in most patients, with JAK inhibitors being the primary pharmacologic treatment option, but alternative therapies and non-pharmacologic approaches may also be considered, and novel combination therapies are being explored. [Read the Full Post]

New therapies in non-small cell lung cancer with EGFR exon 20 insertion mutations

68 | Mar 31 2023

The review identified promising therapies for NSCLC with EGFR exon 20 insertion mutations, but further comparative studies with larger sample sizes and better design are needed to confirm their efficacy. [Read the Full Post]

Contact Sensitization and Phototoxic and Photoallergic Potential of Tirbanibulin 1% Ointment in Healthy Volunteers

41 | Mar 30 2023

The results of the three phase 1 studies suggest that tirbanibulin 1% ointment is safe for topical application in the treatment of actinic keratosis, without any evidence of sensitization or phototoxic or photoallergic potential in healthy adults. [Read the Full Post]

Inhibition of the epigenetically activated miR-483-5p/IGF-2 pathway results in rapid loss of meningioma tumor cell viability

48 | Mar 30 2023

The study found that targeting the autocrine miR-483/IGF-2 stimulation and IGF-2 pathway may provide a viable treatment option for meningioma. [Read the Full Post]

Identification of Inhibitors of Tubulin Polymerization Using a CRISPR-Edited Cell Line with Endogenous Fluorescent Tagging of β-Tubulin and Histone H1

68 | Mar 29 2023

The study presents a novel approach for identifying tubulin polymerization inhibitors using CRISPR-edited cells with fluorescently tagged endogenous β-tubulin and nuclear protein, enabling the screening of large compound libraries containing diverse chemical families for the discovery of new and effective therapies for cancer treatment. [Read the Full Post]

The outcome of ibrutinib-based regimens in relapsed/refractory central nervous system lymphoma and the potential impact of genomic variants

47 | Mar 28 2023

This study suggests that ibrutinib-based therapy is effective and safe for treating r/r CNSL patients, and patients with less genomic complexity, especially with regard to TMB, may benefit more from ibrutinib regimens. [Read the Full Post]

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report

64 | Mar 26 2023

This case report highlights the possibility of sustained response off therapy after discontinuing fostamatinib in chronic immune thrombocytopenia. [Read the Full Post]

Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study

141 | Mar 22 2023

This study identified the metabolomic profile and potential therapeutic effects of quercetin and its metabolites in cognitive impairment and Parkinson's disease, but further research is needed to confirm these findings in vivo and address potential adverse effects. [Read the Full Post]

Managing Vibration Training Safety by Using Knee Flexion Angle and Rating Perceived Exertion

120 | Mar 22 2023

This study found that a knee flexion angle of approximately 110 degrees is most effective in reducing vibration transmissibility during whole-body vibration exercise, while also observing a positive correlation between the rating of perceived exertion and the platform-to-head transmissibility. [Read the Full Post]

Mechanisms of paeoniaceae action as an antidepressant

44 | Mar 22 2023

Paeoniflorin (PF) has been shown to have multiple mechanisms through which it exerts its antidepressant effects, including increasing the levels of monoamine neurotransmitters, inhibiting the HPA axis, promoting neuroprotection, enhancing neurogenesis in the hippocampus, and elevating levels of BDNF. [Read the Full Post]

Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach

88 | Mar 21 2023

The research developed an inhalable EGCG nano-liposome formulation with desirable properties and demonstrated its potential effectiveness in treating PAH by inhibiting the TGFβ pathway. [Read the Full Post]

WP1130 relieves septic shock in mice by inhibiting NLRP3 inflammasome activation

57 | Mar 20 2023

WP1130 specifically inhibits NLRP3 inflammasome activation and alleviates septic shock in mice. [Read the Full Post]

USP9x promotes CD8 + T-cell dysfunction in association with autophagy inhibition in septic liver injury

67 | Mar 20 2023

This study suggests that USP9x inhibition could be a potential therapeutic target for septic liver injury by promoting CD8+ T-cell function via autophagy regulation. [Read the Full Post]

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy

116 | Mar 18 2023

The study identified PIM kinase as a potential target for the development of novel treatments for alveolar echinococcosis, and demonstrated the utility of high-throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. [Read the Full Post]

High-Throughput Screening Assay Identifies Berberine and Mubritinib as Neuroprotection Drugs for Spinal Cord Injury via Blood-Spinal Cord Barrier Protection

58 | Mar 18 2023

The study developed a high-throughput screening assay to identify candidate drugs that protect the blood-brain spinal cord barrier function and demonstrated the neuroprotective effect of berberine and mubritinib after spinal cord injury. [Read the Full Post]

Mubritinib enhanced the inhibiting function of cisplatin in lung cancer by interfering with mitochondrial function

45 | Mar 18 2023

Mubritinib can target mitochondrial electron transport chain complexes and disrupt mitochondrial function, ultimately inducing oxidative stress and increasing ROS levels, leading to its antitumor effect in lung cancer. [Read the Full Post]

Targeting fibroblast growth factor receptors causes severe craniofacial malformations in zebrafish larvae

92 | Mar 16 2023

The study investigated the effects of mutated fgfr2 sa10729 allele in zebrafish on cartilage and bone formation, and found that pharmacological targeting of FGFR1-4 kinase signaling causes severe craniofacial malformations, while abrogation of FGFR2 kinase signaling alone does not induce craniofacial skeletal abnormalities. [Read the Full Post]

Dishevelled 2 regulates cancer cell proliferation and T cell mediated immunity in HER2-positive breast cancer

41 | Mar 15 2023

The study demonstrated the potential immune regulatory role of DVL2 proteins in HER2+ breast cancer, and suggested further investigation of DVL paralogs as potential therapeutic targets. [Read the Full Post]

Hypoxia-induced YAP activation and focal adhesion turnover to promote cell migration in mesenchymal TNBC cells

113 | Mar 08 2023

The study suggests that hypoxia-induced YAP activation is positively associated with mesenchymal TNBC cell migration and may be a novel factor responsible for promoting the aggressive behavior of TNBC cells under hypoxic conditions. [Read the Full Post]

Role of pericytes in the development of cerebral cavernous malformations

71 | Feb 25 2023

Pericytes in cerebral cavernous malformation (CCM) are essential for lesion development and fibronectin intervention may provide a novel target for therapeutic intervention, as pericyte function inhibition and increased fibronectin expression were found to be linked to CCM lesion development. [Read the Full Post]

Nanodroplet-enhanced sonodynamic therapy potentiates immune checkpoint blockade for systemic suppression of triple-negative breast cancer

130 | Feb 25 2023

The combination of STING activation, hypoxia relief, and sonodynamic therapy with anti-PD-L1 therapy using an O2-filled nanodroplet shows strong efficacy in suppressing triple-negative breast cancer growth and improving therapeutic outcome by promoting mature DCs, inducing immunogenic cell death, and enhancing tumor infiltration of CTLs. [Read the Full Post]

Case report: Ponatinib as a bridge to CAR-T cells and subsequent maintenance in a patient with relapsed/refractory Philadelphia-like acute lymphoblastic leukemia

77 | Feb 22 2023

A young patient with relapsed/refractory Ph-like ALL was successfully treated with chimeric antigen receptor T (CAR-T) cells after bridging with compassionate-use ponatinib and low-dose prednisone, and maintained with low-dose ponatinib, resulting in measurable residual disease negativity and B-cell aplasia 20 months later, marking this as the first reported use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

215 | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Transferrin receptor 2 deficiency promotes macrophage polarization and inflammatory arthritis

121 | Feb 18 2023

Tfr2 deletion results in increased joint swelling and bone erosion in a K/BxN serum-transfer arthritis model, which may be due to Tfr2's role in suppressing pro-inflammatory M1-like polarization in macrophages. [Read the Full Post]

Zearalenone and its metabolite exposure directs oestrogen metabolism towards potentially carcinogenic metabolites in human breast cancer MCF-7 cells

74 | Feb 11 2023

Mycoestrogens increase the production of CYP1B1-mediated oestrogen catechol metabolites, directing the biotransformation of E2 towards 4-OHE2, a crucial factor in oestrogen-induced tumour initiation. [Read the Full Post]

Synthesis and antiproliferative activity evaluation of B-norcholesterol-6-amide compounds

69 | Feb 10 2023

The study found that introducing chloroalkyl acyl groups into the 6-position of 6-amino-B-norcholesterol greatly enhanced the cytotoxicity of the resulting B-norcholesterol-6-amide compounds, with compound 20 having an IC50 value of 3.9 μM on HeLa cells. [Read the Full Post]

Small Bowel Lipomatosis: An Unusual Radiological Finding in Patients With Renal Cell Cancer on Pazopanib

38 | Feb 06 2023

The study found that small bowel lipomatosis is a unique finding in patients with advanced renal cell carcinoma receiving pazopanib, but is not seen with other tyrosine kinase inhibitors. [Read the Full Post]

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial

63 | Feb 03 2023

A study of 45 patients with metastatic colorectal cancer treated with regorafenib found that KRAS mutations in tissue or plasma did not impact its efficacy, but higher levels of circulating cell-free DNA were associated with poorer prognoses. [Read the Full Post]

Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?

64 | Feb 02 2023

The treatment landscape for advanced hepatocellular carcinoma (HCC) has become complex with the introduction of immune checkpoint inhibitors (ICIs), and a number of second-line therapies, with rechallenge with ICIs being an attractive alternative, but requires careful evaluation and the identification of predictive biomarkers is an urgent matter to address in HCC research. [Read the Full Post]

VEGFR-TKI treatment for radiation-induced brain injury after gamma knife radiosurgery for brain metastases from renal cell carcinomas

42 | Jan 23 2023

Ryuichi Noda et al. demonstrated the therapeutic effects of vascular endothelial growth factor receptor tyrosine kinase inhibitors on radiation-induced brain injury in patients with brain metastases from renal cell carcinoma treated via gamma knife radiosurgery. [Read the Full Post]

Treatment and Implications of Vascular Endothelial Growth Factor Inhibitor-Induced Blood Pressure Rise: A Clinical Cohort Study

77 | Jan 22 2023

Daan C H van Dorst et al. thought that both calcium channel blockers and renin-angiotensin system inhibitors were effective antihypertensive treatments. [Read the Full Post]

Preclinical Evaluation of Trabectedin in Combination With Targeted Inhibitors for Treatment of Metastatic Uveal Melanoma

56 | Jan 18 2023

Kseniya Glinkina et al. found that trabectedin alone or in combination with cabozantinib inhibited tumor growth in PDX UM mouse models. [Read the Full Post]

Integrated bioinformatics analysis and experimental validation reveals fatty acid metabolism-related prognostic signature and immune responses for uterine corpus endometrial carcinoma

92 | Jan 18 2023

Chenrui Guo et al. found that a FAMGs-based risk signature might be considered as an independent prognostic indicator to predict UCEC prognosis. [Read the Full Post]

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients

67 | Jan 17 2023

Tingting Zhao et al.revealed histone modification-associated prognostic genes to construct the HMAG signature, aiming to provide a new insight into prognosis prediction and precise clinical treatment. [Read the Full Post]

Integrative analysis reveals clinically relevant molecular fingerprints in pancreatic cancer

83 | Jan 17 2023

Libin Song et al. found that PCCLs with mutations in CDKN2A, TP53, and SMAD4 were more sensitive to certain anti-cancer drugs. [Read the Full Post]

Crizotinib Nanomicelles Synergize with Chemotherapy through Inducing Proteasomal Degradation of Mutp53 Proteins

54 | Jan 10 2023

Tianxiang Yi et al. suggested a novel combination therapeutic strategy for targeting p53 cancer in further clinical application. [Read the Full Post]

Single-cell profiling reveals molecular basis of malignant phenotypes and tumor microenvironments in small bowel adenocarcinomas

65 | Jan 06 2023

Jingwei Yang et al. showed that the duodenal subtype of SBA exhibited molecular features more similar to gastric cancer whereas jejunal subtype of SBA more similar to colorectal cancer. [Read the Full Post]

Ferroptosis-related differentially expressed genes serve as new biomarkers in ischemic stroke and identification of therapeutic drugs

82 | Jan 05 2023

Yinjiang Zhang et al. found that ferroptosis played a critical role in the diversity and complexity of the IS immune microenvironment. [Read the Full Post]

ZD6474 Attenuates Fibrosis and Inhibits Neovascularization in Human Pterygium by Suppressing AKT-mTOR Signaling Pathway

104 | Jan 05 2023

Wenting Liu et al. found that ZD6474 was more effective than MMC in reducing fibrosis and EMT in HPFs. [Read the Full Post]

Utilizing inner filter effect in resonance Rayleigh scattering technique: a case study with silver nanocubes as RRS probe and several analytes as absorbers

44 | Jan 04 2023

Rasoul Gheitaran et al. found that the newly developed IFE mechanism could be employed as an attractive and highly efficient analytical technique for measuring different analytes. [Read the Full Post]

Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma

46 | Jan 04 2023

Kohei Kobatake et al. thought that investigating RM on pre-treatment CT scans could effectively predict worse prognosis. [Read the Full Post]

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial

0 | Jan 01 2023

C Dinkic et al. thought that pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. was a feasible regimen for patients with recurrent platinum-resistant EOC. [Read the Full Post]

Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients

76 | Dec 31 2022

Karen E Anderson et al. explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients. [Read the Full Post]

Oral Side Effects in Patients with Metastatic Renal Cell Carcinoma Receiving the Antiangiogenic Agent Pazopanib-Report of Three Cases

33 | Dec 31 2022

Erofili Papadopoulou et al. thought that gingival bleeding and MRONJ might develop as oral side effects of pazopanib use. [Read the Full Post]

Optimizing the value of lenalidomide maintenance by genetic profiling - an analysis of 556 Myeloma XI trial patients

80 | Dec 30 2022

Aikaterini Panopoulou et al. found that extended genetic profiling identified patients deriving exceptional benefit from Len maintenance. [Read the Full Post]

The Economic Burden of Chronic Myeloid Leukemia in Patients with Later Lines: Findings from a Real-World Analysis in Italy

95 | Dec 30 2022

Massimo Breccia et al. suggested that further efforts were needed to improve the therapeutic management of later lines of CML. [Read the Full Post]

Attenuated Dose Dasatinib in Newly Diagnosed Chronic Myeloid Leukemia Chronic Phase Patients in India

24 | Dec 29 2022

Rayaz Ahmed et al. thought that low dose dasatinib was safe and effective as an upfront therapy in CML-CP. [Read the Full Post]

Desensitization Protocol to Lenalidomide: An Effective and Safe Treatment Modality for Delayed Hypersensitivity-induced Rash in Patients with Multiple Myeloma

138 | Dec 29 2022

Oded Shamriz et al. thought that desensitization to lenalidomide was safe and effective. [Read the Full Post]

Combined use of dasatinib and quercetin alleviates overtraining-induced deficits in learning and memory through eliminating senescent cells and reducing apoptotic cells in rat hippocampus

56 | Dec 28 2022

Chenkang Wang found that D+Q alleviated overtraining-induced deficits in learning and memory through elimination of senescent cells and reduction of apoptotic cell number. [Read the Full Post]

Comprehensive Analysis of Circular RNA Expression Profiles in Gefitinib-Resistant Lung Adenocarcinoma Patients

79 | Dec 28 2022

Junyong Zou et al. validated that upregulations of hsa_circ_0030591 and hsa_circ_0040348 might play key roles in EGFR-TKI resistance and thus serving as candidates for biomarker. [Read the Full Post]

Clinical impact of minimal residual disease and genetic subtypes on the prognosis of childhood acute lymphoblastic leukemia

94 | Dec 27 2022

Chih-Hsiang Yu et al. found that MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. [Read the Full Post]

Preformulation studies of dovitinib free base: Solubility, lipophilicity and stability

22 | Dec 26 2022

Suppakan Sripetch et al. found that dovitinib was most stable at pH 4 in the phosphate buffer species. [Read the Full Post]

Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984

33 | Dec 25 2022

Joseph W Kim et al. found that cediranib combined with olaparib improved rPFS compared with olaparib alone in men with mCRPC. [Read the Full Post]

DNA-Encoded Library Screening To Inform Design of a Ribonuclease Targeting Chimera (RiboTAC)

20 | Dec 25 2022

Samantha M Meyer et al. demonstrated that DEL could be used to identify compounds that bound and recruited proteins with effector functions in heterobifunctional compounds. [Read the Full Post]

A mitophagy-related gene signature associated with prognosis and immune microenvironment in colorectal cancer

133 | Dec 24 2022

Cong Zhang et al. developed a novel mitophagy-related gene signature that could be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients. [Read the Full Post]

Discovery of Clinical Candidate AZD0095, a Selective Inhibitor of Monocarboxylate Transporter 4 (MCT4) for Oncology

19 | Dec 24 2022

Frederick W Goldberg et al. thought that MCT4 inhibition might be of interest for immuno-oncology. [Read the Full Post]

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

74 | Dec 23 2022

Keiko Imamura et al. found that the treatment-responsive patients could be distinguished by lower levels of plasma NFL. [Read the Full Post]

Safety profile of tyrosine kinase inhibitors used in non-small-cell lung cancer: An analysis from the Italian pharmacovigilance database

99 | Dec 22 2022

Maria Antonietta Barbieri et al. suggested that more attention should be paid to the occurrence of serious life-threatening ADRs including respiratory failure, interstitial lung disease, and cardiogenic shock, especially in young patients. [Read the Full Post]

KMT2D deficiency drives lung squamous cell carcinoma and hypersensitivity to RTK-RAS inhibition

67 | Dec 22 2022

Yuanwang Pan et al identified KMT2D as a pivotal epigenetic modulator for LUSC oncogenesis and suggested that KMT2D loss renders LUSC therapeutically vulnerable to RTK-RAS inhibition. [Read the Full Post]

Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): a rapidly evolving strategy

22 | Dec 21 2022

Mohammadsaleh Jahangir et al. offered a glimpse into the well-determined prognostic factor associated with the clinical response of RCC patients to PD-1/PD-L1 blockade therapy. [Read the Full Post]

Comparison of efficacy of roxadustat and erythropoietin for the treatment of renal anemia in patients with chronic kidney disease: a retrospective study

42 | Dec 21 2022

Chen Jin et al. thought that orally administered roxadustat improved hemoglobin levels more than rhEPO in patients with CKD and anemia. [Read the Full Post]

A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis

62 | Dec 20 2022

Rui Chen et al. thought that CLEC5A was a potential prognostic biomarker of diverse cancers and a target for anti-tumor therapy. [Read the Full Post]

Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status

22 | Dec 20 2022

Lucía Carril-Ajuria et al. found that no significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. [Read the Full Post]

Epigenomic and transcriptomic landscaping unraveled candidate repositioned therapeutics for non-functioning pituitary neuroendocrine tumors

28 | Dec 19 2022

B Aydin et al. found that molecular docking simulations, palbociclib, linifanib, trametinib, eplerenone, niguldipine, and zuclopenthixol showed higher binding affinities with hub genes compared to their inhibitors. [Read the Full Post]

Pemigatinib in cholangiocarcinoma with a FGFR2 rearrangement or fusion

25 | Dec 08 2022

Michael H Storandt et al. found that FGFR inhibitors, including pemigatinib, had shown promise in the management of CCA with FGFR2 fusion or rearrangement. [Read the Full Post]

The 8p11 myeloproliferative syndrome: Genotypic and phenotypic classification and targeted therapy

32 | Dec 08 2022

Taotao Li et al. thought that the TKIs might become an 8p11 treatment option as an alternative to hematopoietic stem cell transplantation. [Read the Full Post]

Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)

96 | Dec 07 2022

Chengwei Zhang et al. found that MS4077 (5) and MS4078 (6) potently decreased cellular levels of oncogenic active ALK fusion proteins in a concentration- and time-dependent manner in SU-DHL-1 lymphoma and NCI-H2228 lung cancer cells. [Read the Full Post]

Nanoplastics exposure induces vascular malformation by interfering with the VEGFA/VEGFR pathway in zebrafish (Danio rerio)

76 | Dec 04 2022

Lu Dai et al. found that nanoplastics might induce vascular malformation by regulating VEGFA/VEGFR pathway-related genes at the early developmental stage in zebrafish. [Read the Full Post]

Curcuminoids Inhibit Angiogenic Behaviors of Human Umbilical Vein Endothelial Cells via Endoglin/Smad1 Signaling

16 | Dec 03 2022

Yi-Fan Chou et al. suggested combination treatment with curcuminoids and a semaxanib was therefore expected to reverse semaxanib resistance. [Read the Full Post]

Update on diagnostic approaches and therapeutic strategies in systemic mastocytosis

61 | Nov 30 2022

Deepti H Radia et al. addressed the most topical questions related to diagnostics, classification, new disease entities, treatment and multiparameter prognostic scoring systems. [Read the Full Post]

Development of resistance to FGFR inhibition in urothelial carcinoma via multiple pathways in vitro

80 | Nov 29 2022

Geoffrey A Pettitt et al. indicated a benefit from treatment interruptions or re-treatment following disease relapse in some patients. [Read the Full Post]

Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival

118 | Nov 27 2022

Naseema Gangat et al. suggested a short-term survival benefit associated with anemia response in momelotinib-treated patients with MF. [Read the Full Post]

MPN-379 Matching-Adjusted Indirect Comparison (MAIC) of Pelabresib (CPI-0610) in Combination With Ruxolitinib vs. JAK Inhibitor Monotherapy in Patients With Intermediate or High-Risk Myelofibrosis

129 | Nov 27 2022

Vikas Gupta et al. suggested that MAIC-adjusted improvements observed in SVR35 and TSS50 at Week 24 with pelabresib and ruxolitinib vs. ruxolitinib, fedratinib, or momelotinib monotherapy were consistent with unadjusted comparisons. [Read the Full Post]

Inhibition of focal adhesion turnover prevents osteoblastic differentiation through β-catenin mediated transduction of pro-osteogenic substrate

42 | Nov 26 2022

Otto J Juhl 4th et al. suggested that the observed β-catenin translocation is a result of focal adhesion turnover, providing evidence for a focal adhesion initiated, β-catenin mediated mechanism of substrate surface signal transduction. [Read the Full Post]

The efficacy and safety analysis of first-line immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma

17 | Nov 23 2022

Xiaoying Qian et al. thought that first-line immunotherapy had promising therapeutic potential in the treatment of PSC. [Read the Full Post]

Hypoxia inducible factor 1α inhibitor induces cell death via suppression of BCR-ABL1 and Met expression in BCR-ABL1 tyrosine kinase inhibitor sensitive and resistant chronic myeloid leukemia cells

28 | Nov 22 2022

Masanobu Tsubaki et al. indicated that HIF-1α regulated BCR-ABL and Met expression and was involved in cell survival in CML cells. [Read the Full Post]

Identification of biomarkers and key pathways in synovial sarcoma cells exposed to anlotinib by integrating bioinformatics analysis and experimental validation

50 | Nov 22 2022

Xiaoli Liu et al. identified biomarkers and key pathways associated with the effects of anlotinib treatment in SS cells. [Read the Full Post]

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations

40 | Nov 12 2022

Iacopo Petrini et al. found that in combination with chemotherapy and lazertinib in NSCLCs who progressed on osimertinib (MARIPOSA-2). [Read the Full Post]

YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

0 | Nov 12 2022

Jiyeon Yun et al. suggested that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Antithrombotic Effects of Fostamatinib in Combination with Conventional Antiplatelet Drugs

35 | Nov 11 2022

Maan H Harbi et al. found that the Syk inhibitor R406 provided mild inhibition of platelet responses induced by atherosclerotic plaque and that this was mildly amplified by aspirin and ticagrelor. [Read the Full Post]

Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review

64 | Nov 04 2022

Christine Martineau et al. thought that adequate management of AEs associated with TRKi in adults should be a prime focus. [Read the Full Post]

Discovery and functional characterization of the oncogenicity and targetability of a novel NOTCH1-ROS1 gene fusion in pediatric angiosarcoma

56 | Nov 04 2022

Payal Jain et al. found that oral entrectinib treatment effectively suppressed the growth of NOTCH-ROS1-driven tumors. [Read the Full Post]

High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs

49 | Nov 04 2022

Doris Kafita et al. found that we could devise novel categorisation of patient tumours, treatment, and prognostic strategies. [Read the Full Post]

Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity

34 | Oct 27 2022

Yasir Y Elamin et al. found that poziotinib was active in EGFR exon 20-mutant NSCLC, although this activity was influenced by insertion location. [Read the Full Post]

HER2 in Non-Small Cell Lung Cancer: A Review of Emerging Therapies

37 | Oct 26 2022

Natalie F Uy et al. summarized recent progress in novel HER2-targeted agents, and projected next steps in advancing treatment for the thousands of patients with HER2 altered NSCLC. [Read the Full Post]

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction

0 | Oct 25 2022

Gang Xie et al. suggested the potential value of PRT in managing osteolytic diseased mediated by osteoclasts. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

0 | Oct 25 2022

Ryo Kanamoto et al. found an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

0 | Oct 20 2022

Cristina Zahonero et al. found that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status [Read the Full Post]

URMC-099 prophylaxis prevents hippocampal vascular vulnerability and synaptic damage in an orthopedic model of delirium superimposed on dementia

60 | Oct 19 2022

Patrick Miller-Rhodes et al. linked post-surgical endothelial activation, microglial MafB immunoreactivity, and synapse loss as key substrates for DSD, all of which could be prevented by URMC-099. [Read the Full Post]

Investigational spleen tyrosine kinase (SYK) inhibitors for the treatment of autoimmune diseases

31 | Oct 18 2022

Su'an Tang et al. provided a background on autoimmune diseases and provided an update on investigational SYK inhibitors. [Read the Full Post]

BDNF and its signaling in cancer

103 | Oct 07 2022

Mohammad Malekan et al. found that the aberrant signaling of BDNF was implicated in various cancers. [Read the Full Post]

ABCB1 and ABCG2 Control Brain Accumulation and Intestinal Disposition of the Novel ROS1/TRK/ALK Inhibitor Repotrectinib, While OATP1A/1B, ABCG2, and CYP3A Limit Its Oral Availability

89 | Oct 07 2022

Wenlong Li et al. found that systemic exposure of repotrectinib was substantially limited by CYP3A activity. [Read the Full Post]

Imatinib induces diastolic dysfunction and ventricular early-repolarization delay in the halothane-anesthetized dogs: Class effects of tyrosine kinase inhibitors

37 | Oct 03 2022

Koki Chiba et al. found that imatinib suppressed ventricular active relaxation and early repolarization, which might suggest the association of mitochondrial dysfunction-associated inhibition of ATP production. [Read the Full Post]

Hepatocellular carcinoma-derived exosomal miRNA-761 regulates the tumor microenvironment by targeting the SOCS2/JAK2/STAT3 pathway

40 | Sep 30 2022

Xiao-Hu Zhou et al. found that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. [Read the Full Post]

Case Report of CCDC149-ALK fusion: a novel genetic alteration and a clinically relevant target in metastatic papillary thyroid carcinoma

30 | Sep 26 2022

Hannah Lee et al. recommend deep mutational sequencing in BRAFV600E-negative, RAIR PTC to identify targetable genetic alterations, including gene fusions, that might result in dramatic therapeutic benefits. [Read the Full Post]

HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET

50 | Sep 25 2022

Tongyue Zhang et al. uncovered functional and prognostic roles for ETV1 in HCC and exposed a positive feedback loop of HGF-ERK1/2-ETV1-c-MET. [Read the Full Post]

An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors

42 | Sep 22 2022

Yingchao Sun et al. focused on the most recent literature that described the development of PDGFRA inhibitors and their use in clinical trials, as well as the potential benefits from different combination therapy strategies. [Read the Full Post]

Delay of endothelial cell senescence protects cerebral barrier against age-related dysfunction: role of senolytics and senomorphics

55 | Sep 16 2022

Jingyuan Ya et al. found that effectively mitigate accumulation of senescent endothelial cells in cerebrovasculature might prevent age-related BBB dysfunction and might be of prophylactic or therapeutic value to extend lifelong health and wellbeing. [Read the Full Post]

Autophagic sequestration of SQSTM1 disrupts the aggresome formation of ubiquitinated proteins during proteasome inhibition

55 | Sep 15 2022

Chenliang Zhang et al. demonstrated that in the early stage of proteasome inhibition, the maturation of the autophagosome was suppressed, which facilitated aggresome formation of misfolded proteins. [Read the Full Post]

Pharmacokinetic/pharmacodynamic modeling of roxadustat's effect on LDL cholesterol in patients in Japan with dialysis-dependent chronic kidney disease and anemia

27 | Sep 12 2022

Akitsugu Takada found that roxadustat could decrease LDL-C independent of statins and sevelamer. [Read the Full Post]

Protein tyrosine kinase 2b inhibition reverts niche-associated resistance to tyrosine kinase inhibitors in AML

35 | Sep 07 2022

Catana Allert et al. suggested that the leupaxin-PTK2B axis played an important role in acquired TKI resistance in AML. [Read the Full Post]

Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer

134 | Sep 06 2022

Yuhong Liu et al. thought that the combined use of tumor organoids and NGS was a potential way to test tumor heterogeneity and predict drug response in ER + BC, which contributed to the development of personalized therapy. [Read the Full Post]

Design, synthesis, and biological evaluation of potent FAK-degrading PROTACs

61 | Sep 03 2022

Qiaohua Qin et al. found that PROTAC A13 could be useful as expand tool for studying functions of FAK in biological system and as potential therapeutic agents. [Read the Full Post]

Differential prognostic impact of stratified additional chromosome abnormalities on disease progression among Malaysian chronic myeloid leukemia patients undergoing treatment with imatinib mesylate

69 | Aug 29 2022

Ismail Siti Mariam et al. concluded that the stratification based on individual ACAs had a differential prognostic impact and might be a potential novel risk predictive system to prognosticate and guided the treatment of CML patients at diagnosis and during treatment. [Read the Full Post]

Nintedanib Induces the Autophagy-Dependent Death of Gastric Cancer Cells by Inhibiting the STAT3/Beclin1 Pathway

48 | Aug 25 2022

Hui Zhu et al. showed that nintedanib could inhibit gastric cancer cells' proliferation and EMT process. [Read the Full Post]

FGF2 positively regulates osteoclastogenesis via activating the ERK-CREB pathway

64 | Aug 20 2022

Xin Wen et al. established the importance of FGF2 in bone homeostasis, hinting the potential use of FGF2/ERK/CREB specific inhibitors to fight against bone-related disorders, such as osteoporosis. [Read the Full Post]

Small Molecule Inhibitors of MERTK and FLT3 Induce Cell Cycle Arrest in Human CD8 + T Cells

44 | Aug 15 2022

Richard M Powell et al. found that caution was needed when using potent RTKIs in the context of antitumor immune responses. [Read the Full Post]

A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML

44 | Aug 14 2022

Baohuan Cai et al. demonstrated a novel model for transformation of hematopoietic stem cells by chimeric FGFR1 kinases with the combined effects of direct protein activation by the full-length kinases and transcriptional regulation by the truncated nuclear tnFGFR1 derivative. [Read the Full Post]

Evaluation of the Efficacy of Saracatinib-Loaded Nanoparticles in Lymphatic Metastases of HNSCC with the Aid of Bioluminescence Imaging

49 | Aug 13 2022

Liwei Lang et al. showed great potential to evaluate treatments on metastatic diseases with the aid of bioluminescent technology. [Read the Full Post]

Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline

100 | Aug 01 2022

Navneet Singh et al. thought that for patients with an anaplastic lymphoma kinase rearrangement, a performance status (PS) of 0-2, and previously untreated NSCLC, clinicians should offer alectinib or brigatinib or lorlatinib. [Read the Full Post]

Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy

161 | Jul 30 2022

Pincha Devage Sameera Madushan Fernando et al. found that hesperidin showed therapeutic potential against PM2.5-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis. [Read the Full Post]

Identification of Infigratinib as a Potent Reversible Inhibitor and Mechanism-Based Inactivator of CYP2J2: Nascent Evidence for a Potential In Vivo Metabolic Drug-Drug Interaction with Rivaroxaban

63 | Jul 20 2022

Lloyd Wei Tat Tang et al. reported that INF elicits potent reversible inhibition and MBI of CYP2J2. [Read the Full Post]

Compassionate Use of Ripretinib for Patients With Metastatic Gastrointestinal Stromal Tumors: Taiwan and Hong Kong Experience

198 | Jul 20 2022

Li-Ching Lin et al. thought that ripretinib was generally tolerable, with loss of hair being the most common AE. [Read the Full Post]

Effect of fibroblast growth factor signaling on cumulus expansion in mice in vitro

82 | Jul 19 2022

Takuya Kanke et al. suggested that FGFs, other than FGF8, exert suppressive effected on the cumulus expansion process in mice. [Read the Full Post]

Metastatic pulmonary carcinoids with EML4-ALK fusion response to ALK inhibitors: two case reports and review of literature

153 | Jul 18 2022

Xi Lei et al. recommend alectinib for the first-line treatment of metastatic PC with EML4-ALK fusion. [Read the Full Post]

Comparative Efficacy and Safety of Janus Kinase Inhibitors and Secukinumab in Patients with Active Ankylosing Spondylitis: A Systematic Review and Meta-Analysis

193 | Jul 13 2022

Young Ho Lee suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS40 response rate, followed by upadacitinib 15 mg, secukinumab 150 mg, filgotinib 200 mg, and placebo. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

0 | Jul 13 2022

Feng Li et al. demonstrated a significant merit of the method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab

169 | Jul 08 2022

Francesca Ligorio et al. thought that high CD36 expression predicted worse clinical outcomes in early-stage HER2+ BC treated with trastuzumab-based neoadjuvant therapy. [Read the Full Post]

Reengineering Ponatinib to Minimize Cardiovascular Toxicity

233 | Jul 03 2022

Anna Pavlovna Hnatiuk et al. suggested that ponatinib cardiotoxicity was mediated by a few kinases, some of which were previously unassociated with cardiovascular disease. [Read the Full Post]

Caspase-3-induced activation of SREBP2 drives drug resistance via promotion of cholesterol biosynthesis in hepatocellular carcinoma

155 | Jul 01 2022

Etienne H Mok et al. demonstrated that CSC populations in HCC expanded via CASP3-dependent, SREBP2-mediated cholesterol biosynthesis in response to tyrosine kinase inhibitor therapy and that targeting cholesterol biosynthesis could overcome acquired drug resistance. [Read the Full Post]

Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib

167 | Jun 27 2022

Fabio Scirocchi et al. reported that Cabozantinib might exert an immunostimulatory role by inducing immunogenic stress of prostate cancer cells and directly modulating dendritic cells (DCs). [Read the Full Post]

Survival benefit of using pemetrexed for EGFR mutation-positive advanced non-small-cell lung cancer in a randomized phase III study comparing gefitinib to cisplatin plus docetaxel (WJTOG3405)

117 | Jun 23 2022

Naoki Haratake et al. thought that pemetrexed should be administered without fail as a sequential treatment to improve the prognosis of EGFR-mutated NSCLC as well as like EGFR-tyrosine kinase inhibitors. [Read the Full Post]

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

220 | Jun 15 2022

Soei Gen et al. thought that osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion. [Read the Full Post]

Impact of Smoking on Response to the First-Line Treatment of Advanced ALK-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis

155 | Jun 05 2022

Kehai Lin et al. thought that lorlatinib in never-smokers and low-dose alectinib in smokers could be considered optimal first-line therapy for advanced ALK-positive NSCLC. [Read the Full Post]

A Combination of Cytokine-Induced Killer Cells With PD-1 Blockade and ALK Inhibitor Showed Substantial Intrinsic Variability Across Non-Small Cell Lung Cancer Cell Lines

134 | Jun 03 2022

Yutao Li et al. supported the idea that combination therapies offer significant potential when they are optimized on a patient-by-patient basis. [Read the Full Post]

Complete and durable response to crizotinib in a patient with malignant pleural mesothelioma harboring CD74-ROS1 fusion

152 | Jun 02 2022

Xuehua Xie et al. described a case of MPM with CD74-ROS1 fusion who obtained complete and durable response after receiving crizotinib. [Read the Full Post]

Systemic Treatment Patterns and Outcomes in Patients With EGFR Mutated Non-small Cell Lung Cancer and Leptomeningeal Disease

198 | May 26 2022

Cristina M Merkhofer et.al found that prior exposure to osimertinib appeared to favorably influence the natural history of LM disease. [Read the Full Post]

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis

369 | May 20 2022

Patrick O Perche et al. thought that abrocitinib was an efficacious oral JAK 1 inhibitor recently FDA-approved for patients ≥ 18 years old with moderate-to-severe AD who had not responded to systemic medications or when contraindicated otherwise. [Read the Full Post]

CSF-1R inhibitor, pexidartinib, sensitizes esophageal adenocarcinoma to PD-1 immune checkpoint blockade in a rat model

325 | May 19 2022

Ashten N Omstead et al. showed limited toxicity with significant tumor shrinkage in pexidartinib treated animals compared to controls, single agent and in combination with a PD-1 inhibitor, AUNP-12. [Read the Full Post]

The BCL2 Inhibitor Venetoclax Plus Rituximab Is Active in MYD88 Wild-Type Polyneuropathy With Anti-MAG Antibodies

177 | May 18 2022

Chiara Briani et al. found that Class IV evidence that for a patient with relapsed anti-MAG antibody polyneuropathy, MYD88 wild-type, venetoclax plus rituximab was effective. [Read the Full Post]

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients based on an observational study

230 | May 09 2022

Kadir Eser et al. found that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. [Read the Full Post]

Design, Synthesis, and Antitumor Activity of Erlotinib Derivatives

302 | May 08 2022

Long-Fei Mao et al. suggested that compound 3d suppressed cancer cell proliferation through the EGFR-TK pathway. [Read the Full Post]

Lorlatinib Versus Pemetrexed-Based Chemotherapy in Patients With ALK-rearranged NSCLC Previously Treated With Alectinib

252 | May 08 2022

Yuki Takeyasu et al. showed that clinical outcomes of PEM and LOR after failure of alectinib were similar in patients with ALK-positive NSCLC. [Read the Full Post]

Regorafenib induces the apoptosis of gastrointestinal cancer-associated fibroblasts by inhibiting AKT phosphorylation

226 | May 07 2022

Mingjia Zhang et al. found that regorafenib inhibited the proliferation of CAFs and induced the apoptosis of CAFs in vitro. [Read the Full Post]

Tumor acidity/redox hierarchical-activable nanoparticles for precise combination of X-ray-induced photodynamic therapy and hypoxia-activated chemotherapy

283 | May 07 2022

Beibei Zhang et al. developed a combined therapeutic modality based on an intelligent nanosized platform (DATAT-NPVT) with tumor acidity-activated TAT presenting. [Read the Full Post]

FXR/ASS1 axis attenuates the TAA-induced liver injury through arginine metabolism

158 | May 03 2022

Weilong Hong et al. found that a protective role of the FXR/ASS1 axis in TAA-induced liver injury by targeting arginine metabolism, which might shed light on the development of novel therapeutic approaches for acute liver injury. [Read the Full Post]

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L)

350 | May 02 2022

Hidetoshi Hayashi et al. found that Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR- mutated advanced NSCLC did not meet its primary end point, despite the encouraging efficacy and safety profile of this treatment strategy. [Read the Full Post]

FLT3 mutations in acute myeloid leukemia: a review focusing on clinically applicable drugs

233 | May 02 2022

Jae-Sook Ahn et al. summarized information on clinically available FLT3 inhibitors for the management of AML with FLT3 mutations. [Read the Full Post]

Unique Presentation of Bortezomib-Associated Thrombotic Microangiopathy Responsive to Therapeutic Plasma Exchange and Eculizumab Therapy

241 | Apr 27 2022

Robert C Sterner et al. demonstrated the possible utility of TPE with plasma replacement. [Read the Full Post]

Theratyping of the Rare CFTR Variants E193K and R334W in Rectal Organoid-Derived Epithelial Monolayers

333 | Apr 24 2022

Fabiana Ciciriello et al. proposed that the functional CFTR assay might guide personalized medicine in patients with CF-like clinical manifestations as well as in those carrying rare CFTR mutations. [Read the Full Post]

Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium

177 | Apr 23 2022

Felix Reichel et al. found that the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc. [Read the Full Post]

Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs

394 | Apr 23 2022

Hidekatsu Nakai et al, found that the importance of achieving complete surgery and aiming for cure in the treatment of ovarian cancer and how the use of bevacizumab, olaparib, and niraparib should be individualized. [Read the Full Post]

Iguratimod Inhibits Skin Fibrosis by regulating TGF-β1/Smad Signaling Pathway in Systemic Sclerosis

328 | Apr 22 2022

Xi Xie et al. indicated T614 inhibited dermal fibroblasts activation and skin fibrosis at least partly by regulating TGF-β1/smad pathway in experimental SSc models and might be a promising therapeutic agent for SSc. [Read the Full Post]

A CT-based radiomics model to predict subsequent brain metastasis in patients with ALK-rearranged non-small cell lung cancer undergoing crizotinib treatment

382 | Apr 21 2022

Yongluo Jiang et al. developed a CT-based radiomics model to predict subsequent BM in patients with non-brain metastatic NSCLC undergoing crizotinib treatment. [Read the Full Post]

Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer

590 | Apr 19 2022

Yujun Hao et al. found that the drug combination could be an effective therapeutic approach for PIK3CA helical domain mutant tumors. [Read the Full Post]

CDK4/6 inhibitor enhances the radiosensitization of esophageal squamous cell carcinoma (ESCC) by activating autophagy signaling via the suppression of mTOR

168 | Apr 17 2022

Wen-Jun Qin et al. found that palbociclib improved the radiosensitivity of ESCC in vivo and in vitro, and thus it might be a promising radiosensitization agent for the treatment of ESCC. [Read the Full Post]

Growth factor dependence of the proliferation and survival of cultured lacrimal gland epithelial cells isolated from late-embryonic mice

282 | Apr 02 2022

Yoko Karasawa et al. found that EGF and HGF might function in a cooperative autocrine manner, supporting cell proliferation and survival during LG development in late-embryonic and neonatal mice. [Read the Full Post]

Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial

273 | Mar 31 2022

Joyce F Liu et al. found that combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs. [Read the Full Post]

Immune mechanisms of resistance to cediranib in ovarian cancer

292 | Mar 30 2022

Ganga Gopinathan et al. thought that combination of anti-IL-6 or anti-PD1 in patients might increase activity of VEGFR inhibitors and prolong disease-free survival. [Read the Full Post]

Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats

483 | Mar 27 2022

Ankit Uniyal et al. suggested that tozasertib mediates anti-nociceptive activity by inhibiting aurora kinase-mediated KIF17/mLin10/NR2B signaling. [Read the Full Post]

Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells

439 | Mar 27 2022

On-Yu Hong 1 et al. showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells. [Read the Full Post]

New Approaches for the Synthesis of 2,3,5,6-Tetrahydrobenzo[d]thiazole Derivatives and their Anti- proliferative , c-Met Enzymatic Activity and Tyrosine Kinases Inhibitions

260 | Mar 25 2022

Rafat M Mohareb et al. found that anti-proliferative activity of selected compounds toward cancer cell lines classified according to the disease showed that most compounds exhibited high inhibitions. [Read the Full Post]

Investigational spleen tyrosine kinase (SYK) inhibitors for the treatment of autoimmune diseases

234 | Mar 21 2022

Su'an Tang et al. provided a background on autoimmune diseases and provided an update on investigational SYK inhibitors. [Read the Full Post]

Insulin-like signaling promotes limb regeneration in the Chinese mitten crab (Eriocheir sinensis)

237 | Mar 20 2022

Ju Li et al. identified a conserved insulin-like receptor in E. sinensis, and provided new evidence for the involvement of ILS in the regulation of limb autotomy and regeneration in crustaceans. [Read the Full Post]

What's new in myeloproliferative neoplasia

586 | Mar 19 2022

Stefan Schmidt et al. revealed components of the alarmin complex (S100A8 und S100A9) drove this local sterile inflammation process, which also represented a potential therapeutic target, as the S100A8 and A9 inhibitor Tasquinimod reduced fibrosis in a pre-clinical animal model. [Read the Full Post]

Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture

635 | Mar 19 2022

M C B Lira-Nogueira et al. found that internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. [Read the Full Post]

The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia

517 | Mar 18 2022

Theodoros Karantanos et al. implicated CCRL2 as an MDS/sAML cell growth mediator, partially through JAK2/STAT signaling. [Read the Full Post]

Ponatinib, Lestaurtinib, and mTOR/PI3K Inhibitors Are Promising Repurposing Candidates against Entamoeba histolytica

299 | Mar 17 2022

Monica M Kangussu-Marcolino et al. found that all 26 compounds were active against metronidazole-resistant E. histolytica, and 24 were able to block parasite recrudescence after drug removal. [Read the Full Post]

The effect of danusertib, an Aurora kinase inhibitor, onto the cytotoxicity, cell cycle and apoptosis in pancreatic ductal adenocarcinoma cells

677 | Mar 11 2022

Ismail Ayberk Kirbiyik et al. thought that Aurora kinase inhibitor danusertib might be a potential alternative to the treatment of pancreatic cancers. [Read the Full Post]

Combined Inhibition of Polo-Like Kinase-1 and Wee1 as a New Therapeutic Strategy to Induce Apoptotic Cell Death in Neoplastic Mast Cells

682 | Mar 10 2022

Manuela Mancini et al. showed that repurposing Plk1 or AKA ± Wee1 inhibitors in advanced clinical development for other indications was a therapeutic strategy worthy of being explored, in order to improve the outcome of patients with advanced SM. [Read the Full Post]

FGFR2 Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma

175 | Mar 09 2022

James M Cleary et al. revealed that these FGFR2 EIDs were sensitive to FGFR inhibition in vitro, and patients with these alterations benefited from treatment with FGFR inhibitors in the clinic. [Read the Full Post]

A FAK Inhibitor Boosts Anti-PD1 Immunotherapy in a Hepatocellular Carcinoma Mouse Model

389 | Mar 05 2022

Yuhua Wei et al. suggested that combination of the FAK inhibitor VS4718 and anti-PD1 could be a potential therapy for HCC by improving the immune environment, reducing liver fibrosis and simultaneously preventing PD1 from binding to the increased PD-L1 induced by FAK inhibitor VS4718. [Read the Full Post]

The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM)

278 | Mar 04 2022

Man Lee Yuen et al. showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. [Read the Full Post]

Baricitinib for relapsing giant cell arteritis: a prospective open-label 52-week pilot study

509 | Feb 23 2022

Matthew J Koster et al. showed that in this proof-of-concept study, baricitinib at 4 mg/day was well tolerated and discontinuation of GC was allowed in most patients with relapsing GCA. [Read the Full Post]

Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and psoriasis - A nationwide cohort study from the DANBIO and DERMBIO registries

360 | Feb 22 2022

Alexander Egeberg et al. emphasized that although these diseases had many overlaps in their pathogenesis, there was a need for an individualized treatment approach that considered the underlying disease, patient profile, and treatment history. [Read the Full Post]

The role of fibroblast growth factor receptor (FGFR) protein-tyrosine kinase inhibitors in the treatment of cancers including those of the urinary bladder

178 | Feb 21 2022

Robert Roskoski Jr thought that the FDA approval of erdafitinib for the treatment of urinary bladder cancers might stimulate additional work targeting the many other FGFR-driven neoplasms. [Read the Full Post]

Pro-Inflammatory and Pro-Oxidative Changes During Nilotinib Treatment in CML Patients: Results of a Prospective Multicenter Front-Line TKIs Study (KIARO Study)

413 | Feb 20 2022

Anna Sicuranza et al. showed a pro-inflammatory/pro-oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib. [Read the Full Post]

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia

283 | Feb 19 2022

Miklos Egyed et al. showed a high rate of molecular remission without an impaired safety profile. Adverse events, with an occurrence rate of >20%, were as follows: grade 1-2 myelosuppression, gastrointestinal toxicity, rash, constitutional symptoms; grade 3 or 4 toxicities were syncope, pneumonia, hypertension, atrial fibrillation, neutropenia and thrombocytopenia. [Read the Full Post]

Acalabrutinib CYP3A mediated Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to inform dose adjustment strategy

218 | Feb 18 2022

Buyun Chen et al. suggested that current PBPK model could be used to propose dose adjustment for drug interactions via CYP3A. [Read the Full Post]

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial

0 | Feb 08 2022

C Dinkic et al. found that Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. [Read the Full Post]

The Relationship Between the Distribution of Training Intensity and Performance of Kayak and Canoe Sprinters: A Retrospective Observational Analysis of One Season of Competition

160 | Feb 07 2022

Manuel Matzka et al. showed that this seasonal analysis of the effects of training revealed extensive inter-individual variability. [Read the Full Post]

Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response

378 | Jan 31 2022

Sean P Korpela et al. found that heterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells. [Read the Full Post]

HER2 Tyrosine Kinase Inhibitors in the Sensitization to Cancers Resistant to HER2 Antibodies

367 | Jan 30 2022

Heena Singla et al. thought that act synergistically with the HER2-antibody resulting in an additive clinical response in patients. [Read the Full Post]

Experiences of running a stratified medicine adaptive platform trial: Challenges and lessons learned from 10 years of the FOCUS4 trial in metastatic colorectal cancer

294 | Jan 30 2022

Louise C Brown et al. found that adaptive stratified medicine platform studies were feasible in common cancers but present challenges. [Read the Full Post]

Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events

157 | Jan 10 2022

Hideki Imano et al. thought that activation of inflammasomes contributes to the idiosyncratic reactions associated with semaxanib and sorafenib. [Read the Full Post]

VEGFR 2 in vascular smooth muscle cells mediates H 2 S-induced dilation of the rat cerebral basilar artery

194 | Jan 10 2022

Jinhua Chen et al. found that H2S-induced CBA dilation and reduction of [Ca2+]i in VSMCs occured by acting on VEGFR2. [Read the Full Post]

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

257 | Jan 07 2022

Hui-Jun Wang et al. found that Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib. [Read the Full Post]

Fibroblast growth factor (FGF), FGF receptor (FGFR), and cyclin D1 (CCND1) DNA methylation in head and neck squamous cell carcinomas is associated with transcriptional activity, gene amplification, human papillomavirus (HPV) status, and sensitivity to tyrosine kinase inhibitors

273 | Jan 05 2022

Yilin Bao et al. found significant correlations of DNA methylation of specific CpG sites with response to the FGFR1/3-selective inhibitors PD 173074 and AZD4547, predominantly within the transcription start site of CCND1. [Read the Full Post]

CYT387 Inhibits the Hyperproliferative Potential of Fibroblast-like Synoviocytes via Modulation of IL-6/JAK1/STAT3 Signaling in Rheumatoid Arthritis

432 | Jan 04 2022

Susmita Srivastava et al. found that CYT387 inhibits proliferation, migration, and pathogenic diseased potential of FLS isolated from adjuvant-induced arthritic (AA) rats via targeting IL-6/JAK1/STAT3 signaling cascade. [Read the Full Post]

A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer

463 | Jan 03 2022

Sukhmani K Padda et al. showed that the JAK1/2 and TBK1 inhibitor momelotinib in combination with erlotinib did not appear to enhance benefit over the historical data of erlotinib monotherapy in patients with EGFR-mutated NSCLC. [Read the Full Post]

Collagen XV Promotes ER Stress-Induced Inflammation through Activating Integrin β1/FAK Signaling Pathway and M1 Macrophage Polarization in Adipose Tissue

357 | Jan 02 2022

Changxing Li et al. provided new ideas for solving the problems of adipose tissue metabolism disorders caused by abnormal accumulation of ECM. [Read the Full Post]

Safety of Anlotinib Capsules Combined with PD-1 Inhibitor Camrelizumab in the Third-Line Treatment of Advanced Non-Small-Cell Lung Cancer and Their Effect on Serum Tumor Markers

285 | Dec 30 2021

Yinhua Wang et al. found that application of anlotinib capsules combined with the PD-1 inhibitor (camrelizumab) in the third-line treatment of advanced NSCLC could effectively reduce the levels of serum tumor markers and cancer fatigue degree of patients. [Read the Full Post]

Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib

222 | Dec 30 2021

Fangling Hu et al. suggested that anlotinib could potentially treat HNSCC. [Read the Full Post]

Protective Effects of Hif2 Inhibitor PT-2385 on a Neurological Disorder Induced by Deficiency of Irp2

283 | Dec 29 2021

Jiaqi Shen et al. found that Irp2 depletion-induced Hif2α was, in vivo, in charge of the switch between OXPHOS and glycolysis. [Read the Full Post]

YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

0 | Dec 20 2021

Jiyeon Yun et al. suggested that YH25448 was a promising third-generation EGFR inhibitor, which might be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Cardiac Safety Assessment of Lazertinib: Findings From Patients With EGFR Mutation-Positive Advanced NSCLC and Preclinical Studies

464 | Dec 19 2021

Seong Bok Jang et al. indicated that lazertinib was not associated with increased cardiac risk. [Read the Full Post]

Drug repurposing for COVID-19 using computational screening: Is Fostamatinib/R406 a potential candidate?

519 | Dec 18 2021

Sovan Saha et al. found that Fostamatinib (R406 as its active promoiety) may also be considered as one of the potential candidates for further clinical trials in pursuit to counter the spread of COVID-19. [Read the Full Post]

Glucocorticoid resistance is reverted by LCK inhibition in pediatric T-cell acute lymphoblastic leukemia

0 | Dec 12 2021

Valentina Serafin et al. found that GC-sensitive cells cultured with IL-4 displayed an increased resistance to dexamethasone, whereas the inhibition of IL-4 signaling could increase GC-induced apoptosis in resistant cells. [Read the Full Post]

Detection of gene mutations and gene-gene fusions in circulating cell-free DNA of glioblastoma patients: an avenue for clinically relevant diagnostic analysis

523 | Dec 11 2021

Vikrant Palande et al. found that new avenues for precision medicine in GBM, using non-invasive liquid biopsy diagnostics to assess personalized patient profiles. Moreover, repeated detection of druggable targets over the course of the disease may provide real-time information on the evolving molecular landscape of the tumour. [Read the Full Post]

Detection of gene mutations and gene-gene fusions in circulating cell-free DNA of glioblastoma patients: an avenue for clinically relevant diagnostic analysis

483 | Dec 10 2021

Vikrant Palande et al. suggested that integrated analysis of cfDNA plasma concentration, gene mutations and gene-gene fusions could serve as a diagnostic modality for distinguishing GBM patients who might benefit from targeted therapy. [Read the Full Post]

Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial

545 | Dec 02 2021

Xiuning Le et al. found that Poziotinib demonstrated antitumor activity in previously treated patients with HER2 exon 20 insertion NSCLC. [Read the Full Post]

Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer

545 | Dec 02 2021

J Robert McCorkle et al. thought that lapatinib and poziotinib combined with paclitaxel synergizes to inhibit the proliferation of ABCB1-overexpressing ovarian cancer cells in vitro. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

0 | Dec 01 2021

Ryo Kanamoto et al. found an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction

815 | Nov 30 2021

Gang Xie et al. suggested the potential value of PRT in managing osteolytic diseases mediated by osteoclasts. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

0 | Nov 26 2021

Cristina Zahonero et al. found that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status. [Read the Full Post]

MLK3 mediates impact of PKG1α on cardiac function and controls blood pressure through separate mechanisms

770 | Nov 25 2021

Timothy D Calamaras et al. suggested augmenting MLK3 kinase activity could preserve LV function in HF but avoid hypotension from PKG1α activation. [Read the Full Post]

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury

0 | Nov 24 2021

Maria Kost-Alimova et al. suggested fostamatinib as a repurposing drug candidate for ALI. [Read the Full Post]

Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations

796 | Nov 14 2021

Brion W Murray et al. thought that repotrectinib was the most potent inhibitor of wild-type TRKA/B/C fusions and was more potent than selitrectinib against all tested resistance mutations. [Read the Full Post]

Translational Strategies for Repotrectinib in Neuroblastoma

668 | Nov 14 2021

Tara J O'Donohue et al. demonstrated that repotrectinib had antitumor activity in genotypically diverse neuroblastoma models. [Read the Full Post]

Construction of a ceRNA Network and Analysis of Tumor Immune Infiltration in Pancreatic Adenocarcinoma

487 | Nov 12 2021

Jingjing Xiao et sl. suggested that the IC50 values of gemcitabine in PAAD were not significantly different between the high and low risk groups. [Read the Full Post]

The Circadian Rhythms of STAT3 in the Rat Pineal Gland and Its Involvement in Arylalkylamine-N-Acetyltransferase Regulation

522 | Nov 09 2021

Simona Moravcová et al. suggested that the higher nocturnal endogenous level of STAT3 in the pineal gland decelerated or hampered the process of NA-induced AANAT activation or affected the AANAT enzyme stability. [Read the Full Post]

ALK Rearrangement in Small-Cell Lung Cancer and Durable Response to Alectinib: A Case Report

338 | Nov 04 2021

Ning Sun et al. found that the allele frequency of ALK rearrangement and RB1 and TP53 mutations in plasma circulating tumor DNA decreased with the reduction in tumor size. [Read the Full Post]

FAK-targeting PROTAC demonstrates enhanced antitumor activity against KRAS mutant non-small cell lung cancer

508 | Nov 03 2021

Jinyuan Liu et al. thought that PROTACs might serve as promising therapeutic agents for the intractable NSCLC harboring KRAS mutations. [Read the Full Post]

Crosstalk between Cancer Cells and Fibroblasts for the Production of Monocyte Chemoattractant Protein-1 in the Murine 4T1 Breast Cancer

457 | Nov 01 2021

Mayu Imamura et al. thought that although cancer cells had the capacity to crosstalk with fibroblasts via PDGFs, this crosstalk did not play a major role in MCP-1 production or cancer progression in this model. [Read the Full Post]

ZCCHC14 regulates proliferation and invasion of non-small cell lung cancer through the MAPK-P38 signalling pathway

784 | Oct 25 2021

Xiuying Shi et al. found that ZCCHC14 could regulate proliferation and invasion of NSCLC through the P38 pathway. [Read the Full Post]

Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages

840 | Oct 24 2021

Robin C Su et al. discovered that through a high-throughput, unbiased kinase activity profiling strategy, MC-LR-induced phosphorylation events were compared with potential inhibitors, and doramapimod was found to effectively prevent MC-LR-induced inflammatory responses in macrophages. [Read the Full Post]

Roxadustat (FG-4592) protects against ischemia/reperfusion-induced acute kidney injury through inhibiting the mitochondrial damage pathway in mice

491 | Oct 21 2021

Mei Zhang et al. found that pretreatment with FG-4592 might effectively prevent kidney from IRI possibly by via diminishing tubular cells injuries and protection of mitochondrial damage pathway. [Read the Full Post]

FMS-Like Tyrosine Kinase 3 Inhibitors for the Treatment of Acute Myeloid Leukemia

464 | Oct 16 2021

Elli D Novatcheva found that the clinical trials/evidence, similarities, differences, clinical toxicities, and drug interactions relevant to treating clinicians as pertains to 5 FLT3-inhibitors: midostaurin, sorafenib, gilteritinib, crenolanib, and quizartinib. [Read the Full Post]

Modelling hypersensitivity to trastuzumab defines biomarkers of response in HER2 positive breast cancer

670 | Oct 15 2021

Laura Díaz-Gil et al. thought that the identification of trastuzumab response biomarkers might be used to select patients particularly sensitive to facilitate the use of trastuzumab-based therapies and refine follow-up guidelines in patients with HER2+ tumors. [Read the Full Post]

Synthesis and evaluation of FAK inhibitors with a 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine scaffold as anti-hepatocellular carcinoma agents

753 | Oct 12 2021

Hanyi Tan et al. suggested that 16c inhibited the malignant proliferation of hepatocellular carcinoma (HCC) cells through decreasing the phosphorylation in the FAK cascade. [Read the Full Post]

Aspiration Is Associated with Poor Treatment Response in Pediatric Pulmonary Vein Stenosis

985 | Oct 06 2021

Maria Niccum et al. found that potentially modifiable risk factor for poor treatment response in pediatric multi-vessel intraluminal pulmonary vein stenosis in patients with 2-ventricle physiology. [Read the Full Post]

Nintedanib Regulates GRK2 and CXCR2 to Reduce Neutrophil Recruitment in Endotoxin-Induced Lung Injury

642 | Oct 02 2021

Vincent Yi-Fong Su et al. found that the inhibition of adhesion molecules via the activation of GRK2 and the inhibition of p38 MAPK and CXCR2. [Read the Full Post]

Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models

378 | Sep 26 2021

Nicole J Chew et al. found the potential of specific FGFRs, including FGFR4, as targets for precision treatment. [Read the Full Post]

Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

533 | Sep 20 2021

Fabio Forghieri et al. thought that future studies were warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies might have potential clinical utility in NPM1-mutated AML patients. [Read the Full Post]

The Combined Treatment With the FLT3-Inhibitor AC220 and the Complex I Inhibitor IACS-010759 Synergistically Depletes Wt- and FLT3-Mutated Acute Myeloid Leukemia Cells

479 | Sep 20 2021

Xiyuan Lu et al. identified a novel drug combination, AC220 and IACS-010759. [Read the Full Post]

An organ-on-a-chip model for pre-clinical drug evaluation in progressive non-genetic cardiomyopathy

708 | Sep 19 2021

Erika Yan Wang et al. found multifaceted cardioprotective effects of relaxin in restoring contractile function and reducing fibrotic remodeling. [Read the Full Post]

Effects of the Fyn kinase inhibitor saracatinib on ventral striatal activity during performance of an fMRI monetary incentive delay task in individuals family history positive or negative for alcohol use disorder. A pilot randomised trial

598 | Sep 17 2021

Krishna T Patel et al. suggested a possible therapeutic role for Src/Fyn kinase inhibitors in AUD risk. [Read the Full Post]

Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK

752 | Sep 07 2021

Long-Sheng Chang et al. demonstrated the power of the de novo unbiased approach for drug discovery and represented a major step forward in the advancement of therapeutics for the treatment of NF2 related malignancies. [Read the Full Post]

Effect of Dickkopf-1 (Dkk-1) and SP600125, a JNK Inhibitor, on Wnt Signaling in Canine Prostate Cancer Growth and Bone Metastases Wachiraphan Supsavhad 1 2, Bardes B Hassan 1 3,

1374 | Sep 05 2021

Wachiraphan Supsavhad et al. showed that SP600125 had the potential to serve as an alternative adjuvant therapy in some early-stage PCa patients, especially those with high Dkk-1 expression. [Read the Full Post]

Immunotherapy in Hepatocellular Carcinoma

1063 | Aug 27 2021

Claudia A M Fulgenzi et al. thought that in the absence of predictive biomarkers, choice of immunotherapy over kinase inhibitors would continue to remain an empirical exercise, guided by balancing anti-tumour efficacy with toxicity considerations in the individual patient. [Read the Full Post]

Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study

378 | Aug 26 2021

Milind Javle et al. found that infigratinib had promising clinical activity and a manageable adverse event profile in previously treated patients with locally advanced or metastatic cholangiocarcinoma harbouring FGFR2 gene fusions or rearrangements. [Read the Full Post]

Targeted inhibition of FGF19/FGFR cascade improves antitumor immunity and response rate in hepatocellular carcinoma

353 | Aug 26 2021

David Wai Meng Tai et al. suggested that HCC patients with high FGFR2/3 or FGF19/FGFR4 expressing tumors might benefit from a combination infigratinib/FGF401. [Read the Full Post]

Pharmacovigilance analysis of cardiac toxicities associated with targeted therapies for metastatic non-small cell lung carcinoma

855 | Aug 25 2021

Sarah Waliany et al. thought that monitoring for heart failure and arrhythmias should be considered with NSCLC targeted therapies, especially osimertinib. [Read the Full Post]

Tofacitinib Ameliorates Lupus Through Suppression of T Cell Activation Mediated by TGF-Beta Type I Receptor

986 | Aug 20 2021

Qing Yan et al. thought that tofacitinib could suppress T cell activation by upregulating TGFβRI expression, which provided a possible molecular mechanism underlying clinical efficacy of tofacitinib in treating SLE patients. [Read the Full Post]

MiR-221 confers lapatinib resistance by negatively regulating p27 kip1 in HER2-positive breast cancer

882 | Aug 16 2021

Thanh Kieu Huynh et al. suggested Src inhibition as a potential strategy to overcome lapatinib resistance. [Read the Full Post]

Inhibition of AKR1B10-mediated metabolism of daunorubicin as a novel off-target effect for the Bcr-Abl tyrosine kinase inhibitor dasatinib

1196 | Aug 09 2021

Neslihan Büküm et al. demonstrated that dasatinib could synergize with Daun in human cancer cells and enhance its therapeutic effectiveness. [Read the Full Post]

Predictors of Response and Survival to Multikinase Inhibitors in Radioiodine Resistant Differentiated Thyroid Cancer

894 | Aug 08 2021

Tiziana Feola et al. provided an overview of the predictive factors for the response and survival of sorafenib and lenvatinib in RR-DTC. [Read the Full Post]

Bruton's tyrosine kinase (BTK) mediates resistance to EGFR inhibition in non-small-cell lung carcinoma

635 | Aug 01 2021

Chi-Tai Yeh et al. suggested that BTK mediated stemness and EMT properties, and inhibition of BTK potentiated the effect of Gefitinib and Osimertinib in NSCLC cells resistant to TKI. [Read the Full Post]

XHL11, a novel selective EGFR inhibitor, overcomes EGFR T790M-mediated resistance in non-small cell lung cancer

470 | Jul 07 2021

Yi Li et al. thought that XHL11 might be developed as a promising EGFR TKI for the therapeutic use of NSCLC patients. [Read the Full Post]

Using JAK inhibitor to treat cytokine release syndrome developed after chimeric antigen receptor T cell therapy for patients with refractory acute lymphoblastic leukemia: A case report

768 | Jun 30 2021

Fu Ming Zi et al. found that Ruxolitinib could be used as an alternative therapeutic approach for severe and refractory CRS without impairing CAR-T amplification and anti-tumor effect. [Read the Full Post]

Suppression of Microgliosis With the Colony-Stimulating Factor 1 Receptor Inhibitor PLX3397 Does Not Attenuate Memory Defects During Epileptogenesis in the Rat

515 | Jun 29 2021

Season K Wyatt-Johnson eal. revealed that PLX3397 did not improve or worsen the memory deficits in rats that sustained pilocarpine-induced SE. [Read the Full Post]

Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia

566 | Jun 28 2021

Catherine C Smith et al. thought that Mutations in CCND3, a gene not commonly mutated in AML, were a novel cause of clinical primary resistance to FLT3 inhibitors in AML and might have sensitivity to CDK4/6 inhibition. [Read the Full Post]

Natural history of Waldenström macroglobulinemia following acquired resistance to ibrutinib monotherapy

1149 | Jun 27 2021

Joshua N Gustine et al. revealed that continuation of ibrutinib until subsequent treatment was associated with improved disease control and clinical outcomes. [Read the Full Post]

Genetic variant within CDK6 regulates immune response to palbociclib treatment

557 | Jun 17 2021

Valentina Serra et al. suggested that the effect of palbociclib treatment might depend on underlying genetically encoded individual immune response as well as the direct response to the drug. [Read the Full Post]

Treatment outcomes of erlotinib plus gemcitabine as late-line chemotherapy in unresectable pancreatic cancer

688 | Jun 16 2021

Takafumi Mie et al. found that benefits of erlotinib plus gemcitabine as late-line chemotherapy were limited, particularly with respect to PFS. [Read the Full Post]

Enteral lorlatinib after alectinib as a treatment option in anaplastic lymphoma kinase-positive non-small cell lung cancer with triple problems: carcinomatous meningitis, poor performance status, and dysphagia-a case report

494 | Jun 16 2021

Kota Sasaki et al. thought that lorlatinib could be a treatment option for patients with ALK-positive NSCLC showing carcinomatous meningitis, poor PS, and dysphagia upon failure of other ALK inhibitor-based treatments. [Read the Full Post]

Impact of tumor growth rate during preceding treatment on tumor response to nivolumab or irinotecan in advanced gastric cancer

592 | Jun 15 2021

K Kato et al. suggested that NIVO treatment was a more favorable option for patients with slow-growing tumors, and NIVO and IRI were similarly recommended for patients with rapid-growing tumors in refractory AGC. TGR and NL emergence during preceding treatment might be helpful for drug selection and warrant further investigation. [Read the Full Post]

YAP/TAZ suppress drug penetration into hepatocellular carcinoma via stromal activation

970 | Jun 15 2021

Kyungjoo Cho et al. indicated that drug delivery into liver cancer was impaired by YAP/TAZ signaling in tumor cells and subsequent activation of stroma by the signaling. [Read the Full Post]

Soyasaponin A 2 Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline Deficient (MCD) Diet-induced Non-alcoholic Steatohepatitis (NASH) Mice

357 | Jun 09 2021

Fei Xiong et al. found that SS-A2 alleviated steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice. [Read the Full Post]

Efficacy of tyrosine kinase inhibitors against lung cancer with EGFR exon 18 deletion: Case report and pooled analysis

956 | Jun 08 2021

Rafael Rubiera-Pebe et al. showed that afatinib was associated with a greater tumor response rate and a longer PFS than the first generation TKIs. [Read the Full Post]

Triazole antifungal use for prophylaxis and treatment of invasive fungal diseases for patients receiving gilteritinib

659 | Jun 08 2021

Muneerah M Aleissa et al. found that concomitant gilteritinib and triazole therapy was feasible and was not associated with clinically meaningful increase in gilteritinib-related AEs. [Read the Full Post]

Analysis of chemotherapy-induced peripheral neuropathy using the Japanese Adverse Drug Event Report database

686 | Jun 02 2021

Misaki Inoue et al. revealed several drugs associated with a high risk for CIPN development. [Read the Full Post]

Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression

846 | May 30 2021

Kun Liu et al. demonstrated that ivacaftor decreased stemness marker gene expressions of GSCs, including CD133, CD44, and Sox2. [Read the Full Post]

The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China

960 | May 28 2021

Jing Ni et al. found that it was feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population could acquire promising efficacy and tolerance. [Read the Full Post]

IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK

431 | May 26 2021

Christine E Lehman et al. found that treatment with BMS754807 and dasatinib, or a FAK inhibitor alone, significantly increased cleaved-PARP in human ex-vivo HNSCC patient tissues demonstrating a potential clinical utility for targeting FAK or the combined targeting of the IGF1R with Src. [Read the Full Post]

ALK-negative lung inflammatory myofibroblastic tumor in a young adult: A case report and literature review of molecular alterations

772 | May 24 2021

Silvia Angela Debonis et al. thought that although there was no standard of care for the treatment of IMT, identifying genomic alterations could help to redefine the management of patients with negative-ALK disease. [Read the Full Post]

Exosomes derived from miR-16-5p-overexpressing keratinocytes attenuates bleomycin-induced skin fibrosis

629 | May 24 2021

Yunyao Bo et al. thought that the localized delivery of miR-16-5p by keratinocytes-derived exosomes might have potential for efficient clinical treatment of skin fibrosis. [Read the Full Post]

Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids

847 | May 17 2021

Silvia Mola et al. found that TAMs were a driving force for MPM growth, progression, and resistance to tazemetostat. [Read the Full Post]

Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer

480 | May 14 2021

Muriel Lainé et al. reported for the first time the anti-tumor activity of lasofoxifene in mouse models of endocrine therapy-resistant breast cancer. [Read the Full Post]

Ibrutinib combinations in CLL therapy: scientific rationale and clinical results

498 | May 01 2021

Natalia Timofeeva et al. found a new standard of care for CLL is expected to emerge from these investigations. [Read the Full Post]

Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease

395 | Apr 30 2021

Philipp von Hundelshausen et al. thought that specific platelet function tests in blood might help to estimate the probability of bleeding of newly developed BTKi. [Read the Full Post]

Paeoniflorin exerts antidepressant-like effects through enhancing neuronal FGF-2 by microglial inactivation

577 | Apr 23 2021

Jie Cheng et al. found that paeoniflorin exhibited neuroprotective and antidepressant effects in mice, which might be mediated by activating neuronal FGF-2/FGFR1 signaling via the inhibition of microglial activation in the hippocampus. [Read the Full Post]

Cediranib Induces Apoptosis, G1 Phase Cell Cycle Arrest, and Autophagy in Non-Small-Cell Lung Cancer Cell A549 In Vitro

533 | Apr 20 2021

Menghuan Guo et al. suggested that CED could induce apoptosis and G1 phase cell cycle arrest in A549 cells. [Read the Full Post]

Optimal Therapies for Recurrent Glioblastoma: A Bayesian Network Meta-Analysis

512 | Apr 20 2021

Wenlin Chen et al. indicated that bevacizumab (BEV) plus CCNU and regorafenib had a higher efficacy on the ORR, 6-m PFS rate and OS, and that BEV monotherapy or BEV combined with active drug therapies was advantageous for the ORR and 6-m PFS rate. [Read the Full Post]

The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells

1073 | Apr 16 2021

Jing Zhang et al. found that Bcl-2 and Bcl-xL negatively modulated MYC-VX-680 synthetic lethality. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

1472 | Apr 15 2021

Christine Song et al. suggested an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition

416 | Apr 13 2021

Narges K Gortany et al.indicated that foretinib might have the therapeutic potential against human GBM which deserve further investigation. [Read the Full Post]

Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function

427 | Apr 09 2021

Tony J Zheng et al. found that TKIs targeting Syk or BTK inhibited central platelet functional responses but might differentially affect protein activities and organization in critical systems downstream of Syk and BTK in platelets. [Read the Full Post]

Pan- and Isoform-specific Inhibition of the Bromodomain and Extra-terminal Proteins and Evaluation of Synergistic Potential With Entospletinib in Canine Lymphoma

0 | Apr 09 2021

Weibo Kong et al. found that Entospletinib did not enhance the inhibitory effects of the pan- or isoform-specific BET. [Read the Full Post]

IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas

437 | Apr 07 2021

Qing Wang et al. found that the treatment of colon tumor cells with IGF-1R inhibitors stimulated p70S6K1 activity via MEK1/2 to promote survival, providing a new strategy for colorectal cancer therapeutics. [Read the Full Post]

Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

1067 | Apr 06 2021

Irene Castellano-Pellicena et al. explored the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. [Read the Full Post]

In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

885 | Apr 04 2021

Congrong Tang et al. thought that the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors might occur. [Read the Full Post]

Current Clinical Investigations in Myelofibrosis

966 | Apr 04 2021

Sangeetha Venugopal et al. provided insight into the novel therapies under clinical evaluation. [Read the Full Post]

Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma

466 | Apr 02 2021

Robert Hanes et al. supported LY2874455 as a better therapy than NVP-BGJ398 for FRS2-amplified liposarcoma, and a clinical trial was warranted. [Read the Full Post]

A Three-Dimensional Organoid Culture Model to Assess the Influence of Chemicals on Morphogenetic Fusion

292 | Mar 22 2021

David G Belair et al. demonstrated the utility of the in vitro fusion assay for identifying chemicals that disrupted human organoid morphogenesis in a scalable format amenable to toxicology screening. [Read the Full Post]

TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma

409 | Mar 22 2021

Lipika Goyal et al. demonstrated that the irreversible FGFR inhibitor TAS-120 provided clinical benefit in patients with resistance to BGJ398 or Debio 1347 and overcomed several FGFR2 mutations in ICC models. [Read the Full Post]

AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development

350 | Mar 19 2021

Xiaofeng Wan et al. thought that activation of the AKT1-CREB-PDGFRα signaling pathway contributed to the tumor growth induced by PTEN deficiency and should be targeted for cancer treatment. [Read the Full Post]

Cardioautonomic control in healthy singleton and twin pregnancies

627 | Mar 16 2021

Victoria L Meah wt al. suggested that individuals with twin pregnancies had greater sympathetic and lower parasympathetic contributions to heart rate and that cardiac, but not vascular, autonomic control was impacted during twin compared to singleton pregnancy. [Read the Full Post]

Immediate Effect of Baricitinib on Arthritis and Biological Disease-Modifying Antirheumatic Drug-Induced Psoriasis-Like Skin Lesions in Two Patients with Rheumatoid Arthritis

811 | Mar 05 2021

Yoshifumi Tada et al. found that baricitinib was initiated because of RA flare and resulted in immediate beneficial effects on arthritis as well as skin lesions. [Read the Full Post]

In-vitro evaluation of the immunomodulatory effects of baricitinib: implication for COVID-19 therapy

845 | Mar 04 2021

Linda Petrone et al. found that exogenous addition of baricitinib decreased the in-vitro SARS-CoV-2-specific response in COVID-19 patients using a whole-blood platform. [Read the Full Post]

Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma

335 | Mar 03 2021

M -L Nairismägi found that the activity of PRN371 had a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. [Read the Full Post]

BTK gatekeeper residue variation combined with cysteine 481 substitution causes super-resistance to irreversible inhibitors acalabrutinib, ibrutinib and zanubrutinib

381 | Mar 01 2021

H Yesid Estupiñán et al. found that reversible inhibitors showed a variable pattern, from resistance to no resistance, collectively demonstrating the structural constraints for different classes of inhibitors, which might affect their clinical application. [Read the Full Post]

The role of acalabrutinib in adults with chronic lymphocytic leukemia

415 | Feb 28 2021

Bita Fakhri et al. demonstrated superiority of the acalabrutinib-containing arms in terms of both efficacy and tolerability. [Read the Full Post]

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial

567 | Feb 19 2021

C Dinkic et al. thought that Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. was a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. [Read the Full Post]

Receptor-interacting protein kinase 2 contributes to host innate immune responses against Fusobacterium nucleatum in macrophages and decidual stromal cells

292 | Feb 18 2021

Ji-Yeon Park et al. showed that Ripk2 signaling appeared to contribute to the F. nucleatum-induced immune response and could be a preventive and therapeutic target against APOs. [Read the Full Post]

The application of nanoparticles in cancer immunotherapy: Targeting tumor microenvironment

771 | Feb 13 2021

Muyue Yang et al. found that the changes of TME at various stages during tumor development are required to be further elucidated so that more individualized nanoplatforms could be designed. [Read the Full Post]

Selective reactivation of STING signaling to target Merkel cell carcinoma

812 | Feb 13 2021

Wei Liu et al. found that targeted delivery and activation of STINGS162A/G230I/Q266I in tumor cells held great therapeutic promise for the treatment of MCC and many other STING-deficient cancers. [Read the Full Post]

Stomatin-like Protein 2 Promotes Tumor Cell Survival by Activating the JAK2-STAT3-PIM1 Pathway, Suggesting a Novel Therapy in CRC

630 | Feb 07 2021

Qiang Liu et al. suggested that SLP-2 controlled the JAK2-STAT3-PIM1 oncogenic pathway, offering a rationale for a novel therapeutic strategy with combined SGI-1776 and TG-101348 in CRC. [Read the Full Post]

Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response

557 | Feb 06 2021

Sean P Korpela 1 et al. found eterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells. [Read the Full Post]

Dual inhibition of FOXM1 and its compensatory signaling pathway decreased the survival of ovarian cancer cells

471 | Feb 05 2021

Dae Woo Lee et al. found that the addition of tipifarnib or rottlerin to inhibit N‑Ras or p‑PKCδ (S664), respectively, inhibited the compensatory signaling pathway response induced by FDI‑6 in HeyA8 cells. [Read the Full Post]

Trichlorocarban induces developmental and immune toxicity to zebrafish (Danio rerio) by targeting TLR4/MyD88/NF-κB signaling pathway

628 | Feb 04 2021

Jiaqi Xu et al. found the underlying molecular mechanisms on TCC-induced developmental and immune toxicity to zebrafish. [Read the Full Post]

Altered TGFβ/SMAD Signaling in Human and Rat Models of Pulmonary Hypertension: An Old Target Needs Attention

283 | Jan 20 2021

Takayuki Jujo Sanada et al. demonstrated considerable discrepancies in TGFβ-SMAD signaling between iPAH and hPAH patients, as well as between patients and rats with experimental PAH. [Read the Full Post]

Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events

248 | Jan 19 2021

Hideki Imano et al. found that activation of inflammasomes contributed to the idiosyncratic reactions associated with semaxanib and sorafenib. [Read the Full Post]

Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules

299 | Jan 16 2021

Christos Vallilas et al. found that alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors). [Read the Full Post]

Kanglexin accelerates diabetic wound healing by promoting angiogenesis via FGFR1/ERK signaling

397 | Jan 15 2021

Yixiu Zhao et al. thought that KLX had the potential to be developed as a topical drug to promote diabetic wound healing. [Read the Full Post]

MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic

662 | Jan 13 2021

Srdan Verstovsek et al.showed that the MOMENTUM Phase III study was designed to confirm and extend observations of safety and clinical activity of MMB. [Read the Full Post]

CYT387, a Novel JAK2 Inhibitor, Suppresses IL-13-Induced Epidermal Barrier Dysfunction Via miR-143 Targeting IL-13Rα1 and STAT3

758 | Jan 13 2021

Yan Zu et al. revealed that the protective effects and the underlying mechanisms of CYT387 in AD, which provided evidence that miR-143 might be a novel therapeutic target for AD. [Read the Full Post]

CB 1 Cannabinoid Receptors Stimulate Gβγ-GRK2-Mediated FAK Phosphorylation at Tyrosine 925 to Regulate ERK Activation Involving Neuronal Focal Adhesions

615 | Jan 12 2021

George D Dalton et al. found that FAK 925 Tyr-P occured concurrently with CB1-stimulated ERK2 activation and required the actin cytoskeleton and Gi/oβγ-GRK2-mediated cross-talk between CB1, integrins, and receptor tyrosine kinases (RTKs). [Read the Full Post]

Mechanotransduction-targeting Drugs Attenuate Stiffness-induced Hepatic Stellate Cell Activation in vitro

583 | Jan 10 2021

Mutsuko Sakai et al. showed that an integrin antagonist and mechanotransduction-targeting drugs reduced stiffness-induced HSC activation in a dose-dependent fashion. [Read the Full Post]

Anlotinib enhances the antitumor activity of radiofrequency ablation on lung squamous cell carcinoma

273 | Jan 08 2021

Wei Zhou et al. proposed a combinative strategy of RFA and anlotinib as a novel approach for successful management of LSCC. [Read the Full Post]

Anlotinib Plus S-1 for Patients with EGFR Mutation-Negative Advanced Squamous Cell Lung Cancer with PS Scores of 2-3 After Progression of Second-Line or Later-Line Treatment

268 | Jan 08 2021

Xiao-Hong Xie et al. thought that advanced SqCLC patients with higher PS scores still benefited from anlotinib and S-1 combination regimen, even after they failed second-line or later-line systemic treatment. [Read the Full Post]

Effects and Mechanism of Action of PX-478 in Oxygen-Induced Retinopathy in Mice

511 | Jan 07 2021

Xiaoyan Pan et al. found that HIF-1α played a main role in OIR and could be considered a therapeutic target in OIR by suppressing downstream angiogenic factors, PX-478 decreasing the retinal avascular area and NV. [Read the Full Post]

EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation

424 | Dec 30 2020

Sehhoon Park et al. reported the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. [Read the Full Post]

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury

495 | Dec 29 2020

Maria Kost-Alimova et al. suggested fostamatinib as a repurposing drug candidate for ALI. [Read the Full Post]

Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer

733 | Dec 23 2020

Hedvig Elfving et al. found that the presence of NTRK fusion genes in non-small cell lung cancer was exceedingly rare. The use of the immunohistochemical NTRK assay would result in a small number of false positive cases. [Read the Full Post]

Clinicopathologic, Genomic, and Protein Expression Characterization of 356 ROS1 Fusion Driven Solid Tumors Cases

659 | Dec 22 2020

Richard S P Huang et al. characterized a large cohort of ROS1 fusionpos NSCLC and non-NSCLC solid tumors and discovered 10 novel ROS1 fusions. [Read the Full Post]

Poziotinib suppresses ovarian cancer stem cell growth via inhibition of HER4-mediated STAT5 pathway

585 | Dec 15 2020

Heejin Lee et al. suggested that HER4 might be a promising therapeutic target for ovarian CSCs, and that poziotinib might be an effective therapeutic option for the prevention of ovarian cancer recurrence. [Read the Full Post]

Poziotinib Inhibits the Efflux Activity of the ABCB1 and ABCG2 Transporters and the Expression of the ABCG2 Transporter Protein in Multidrug Resistant Colon Cancer Cells

501 | Dec 14 2020

Yongchao Zhang et al. showed that poziotinib interacted with the ABCB1 and ABCG2 transporter, suggesting that poziotinib might increase the efficacy of certain chemotherapeutic drugs used in treating MDR CRC. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

1431 | Dec 13 2020

Ryo Kanamoto et al. demonstrated an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis

0 | Dec 12 2020

Alejandro Torres-Hernandez et al. found that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

782 | Dec 08 2020

Cristina Zahonero et al. confirmd that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status (as it was less effective in a PTEN-deleted GBM line). [Read the Full Post]

Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity

952 | Dec 07 2020

Sandeep Kumar et al. demonstrated that MLK3 played an important role in T cell biology, and targeting MLK3 could serve as a potential therapeutic intervention via increasing T cell cytotoxicity in cancer. [Read the Full Post]

A High Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury during the COVID-19 pandemic

359 | Dec 06 2020

Maria Alimova et al. revealed Fostamatinib as a repurposing drug candidate for ALI and provided the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury. [Read the Full Post]

Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells

0 | Nov 24 2020

Diana Cervantes-Madrid et al. showed that repotrectinib was capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibited strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Cases of ROS1-rearranged lung cancer: when to use crizotinib, entrectinib, lorlatinib, and beyond?

657 | Nov 23 2020

Kartik Sehgal et al. described cases of advanced ROS1-rearranged lung cancer receiving crizotinib, entrectinib, and/or lorlatinib in first and later line treatment settings to dissect the current state of evidence supporting management decisions for these patients. [Read the Full Post]

Cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases: an overview of systematic reviews

426 | Nov 21 2020

Vakaramoko Diaby et al. examined evidence on the cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases through a review of systematic reviews on the topic. [Read the Full Post]

Cucurbitacin E and I target the JAK/STAT pathway and induce apoptosis in Sézary cells

1480 | Nov 18 2020

Isabella J Brouwer et al. suggested that STAT3 played a preferential role in the mechanism of action of these cucurbitacins. [Read the Full Post]

Alectinib-Associated Perforated Duodenal Ulcer

395 | Nov 14 2020

Maximilian J Hochmair et al. found that later-line lorlatinib treatment could induce sustained responses in patients with advanced ALK- and ROS1-positive lung cancer. [Read the Full Post]

Defactinib attenuates osteoarthritis by inhibiting positive feedback loop between H-type vessels and MSCs in subchondral bone

573 | Nov 13 2020

Yanjun Hu et al. demonstrated that defactinib inhibited OA by suppressing the positive feedback loop between H-type vessels and MSCs in subchondral bone. [Read the Full Post]

Wu-5, a novel USP10 inhibitor, enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways

457 | Nov 10 2020

Miao Yu et al. demonstrated that Wu-5, a novel USP10 inhibitor, could overcome FLT3 inhibitor resistance and synergistically enhance the anti-AML effect of crenolanib through targeting FLT3 and AMPKα pathway. [Read the Full Post]

Antianemia Drug Roxadustat (FG-4592) Protects Against Doxorubicin-Induced Cardiotoxicity by Targeting Antiapoptotic and Antioxidative Pathways

512 | Oct 26 2020

Guangfeng Long et al.found that the protective effect of FG-4592 on DOX-induced cardiotoxicity possibly through upregulating HIF-1α and its target genes antagonizing apoptosis and oxidative stress. [Read the Full Post]

FLT3 inhibitors in the treatment of Acute Myeloid Leukemia: current status and future perspectives

380 | Oct 20 2020

Adrián Mosquera Orgueira et al.focused on the role of FLT3 mutations in AML, pharmacological features of FLT3 inhibitors, known mechanisms of drug resistance and accumulated evidence for the use of FLT3 inhibitors in different clinical settings. [Read the Full Post]

SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer

544 | Oct 19 2020

Hao Chen et al.found that SHP2 constituted a shared signaling node allowing MBC cells to simultaneously engage a diversity of growth and survival pathways, including those derived from the ECM. [Read the Full Post]

An exon skipping screen identifies antitumor drugs that are potent modulators of pre-mRNA splicing, suggesting new therapeutic applications

635 | Oct 14 2020

Yihui Shi et al.supported the broad potential for the development of agents that targeted the spliceosome for the treatment of cancer and other diseases, as well as new avenues for the discovery of new chemotherapeutic agents for a range of diseases. [Read the Full Post]

A rare maternal gastrointestinal stromal tumor found in the second trimester of pregnancy: A case report

842 | Oct 03 2020

Naoko Tanaka et al. believed that pregnant patients should be managed by a multidisciplinary team with expertise in gastrointestinal tumors and fetal-maternal medicine. [Read the Full Post]

Advances on Synthesis, Derivatization and Bioactivity of Isatin: A Review

344 | Sep 28 2020

Garima Chauhan et al. reviewed the different strategies for the designs and synthesis of several IST based compounds having different biological activities with SAR which could favour further investigation and modification for the development of new and more potent entities. [Read the Full Post]

FGF18-FGFR2 signaling triggers the activation of c-Jun-YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential

298 | Sep 19 2020

Jinglin Zhang et al. highlighted the translational potential of FGFR2-c-Jun-YAP1 axis, which might serve as a prognostic biomarker and therapeutic target for GC. [Read the Full Post]

FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia

504 | Sep 14 2020

Jun Long et al. demonstrated that HDAC8 upregulation was an important mechanism to resist TKIs and promote leukemia maintenance and suggested that combining HDAC8 inhibition with TKI treatment could be a promising strategy to treat FLT3-ITD+ AML and other tyrosine kinase mutation-harboring leukemias. [Read the Full Post]

Structural Basis of Activin Receptor-Like Kinase 2 (R206H) Inhibition by Bis-heteroaryl Pyrazole-Based Inhibitors for the Treatment of Fibrodysplasia Ossificans Progressiva Identified by the Integration of Ligand-Based and Structure-Based Drug Design Approaches

405 | Sep 13 2020

Tomohiro Sato et al. indicated the existence of the additional hydrogen bond via water molecules restricting the attachment point in the pyrazole scaffold [Read the Full Post]

Quizartinib for the treatment of acute myeloid leukemia

512 | Sep 13 2020

Alejandro Garcia-Horton et al. reviewed the mechanism of action, pharmacology, clinical efficacy, and safety of quizartinib, a FLT3 inhibitor, for the treatment of acute myeloid leukemia. [Read the Full Post]

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

0 | Sep 11 2020

Vanita Noronha et al. found that adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC. [Read the Full Post]

Dual inhibition of Src and PLK1 regulate stemness and induce apoptosis through Notch1-SOX2 signaling in EGFRvIII positive glioma stem cells (GSCs)

597 | Sep 09 2020

Xuetao Li et al. indicated that p-Src and PLK1 contributed to cancer stemness in EGFRvIII-positive GSCs by driving Notch1-SOX2 signaling, a finding that had important clinical implications. [Read the Full Post]

IGF2BP1 is a targetable SRC/MAPK-dependent driver of invasive growth in ovarian cancer

612 | Sep 09 2020

Nadine Bley et al. provided a rationale for the therapeutic benefit of combinatorial SRC/MEK inhibition in mesenchymal-like HGSOC. [Read the Full Post]

Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors

492 | Aug 23 2020

Abhay Singh et al. provided a summary of the clinical development of crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib and highlighted current management paradigms, current and evolving clinical information, emerging clinical decision-making and sequencing of therapy in advanced, metastatic, or recurrent ALK-positive NSCLC. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

1227 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

Regorafenib for Metastatic Colorectal Cancer: An Analysis of a Registry-Based Cohort of 555 Patients

796 | Aug 06 2020

Alena Novakova-Jiresova ETAL. found that regorafenib was a safe and active treatment option for a subgroup of patients with mCRC who were progressing after other systemic therapies and maintain good performance status. [Read the Full Post]

Inhibition of FGF2-Mediated Signaling in GIST-Promising Approach for Overcoming Resistance to Imatinib

355 | Aug 05 2020

Sergei Boichuk et al. provided a rationale to evaluate the effectiveness of the inhibitors of FGF-signaling for IM-resistant GISTs. [Read the Full Post]

Inhibition of FGFR Signaling Partially Rescues Osteoarthritis in Mice Overexpressing High Molecular Weight FGF2 Isoforms

379 | Aug 05 2020

Liping Xiao et al. demonstrated that overexpression of the HMWFGF2 isoforms in preosteoblasts resulted in osteoarthropathy that couid be partially rescued by FGFR inhibitor via reduction in activated Wnt signaling. [Read the Full Post]

Comprehensive analyses of immunodynamics and immunoreactivity in response to treatment in ALK-positive non-small-cell lung cancer

389 | Aug 04 2020

Kyoung-Ho Pyo et al. found that ALK-positive tumors progressing on ceritinib was not immunogenic enough to respond to immune checkpoint inhibitors. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

0 | Jul 29 2020

Feng Li et al. demonstrated a significant merit of our method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Effectiveness and Costs Among Rheumatoid Arthritis Patients Treated with Targeted Immunomodulators Using Real-World U.S. Data

794 | Jul 28 2020

Mahdi Gharaibeh et al. showed that the range of patients who were effectively treated with first-line therapy was higher for certain tumor necrosis factor inhibitors and tocilizumab. [Read the Full Post]

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

894 | Jul 22 2020

Cristina Saura et al.showed that N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed. [Read the Full Post]

In vitro and in vivo efficacies of inhibitors of the EGFR/MEK/ERK signaling in the treatment of alveolar echinococcosis

631 | Jul 17 2020

Zhe Cheng et al. demonstrated the potential of EGFR-mediated signaling as a target for the development of novel anti-AE agents. [Read the Full Post]

A Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects

1172 | Jul 15 2020

Yiqing Yang et al. found that PROTACs showed better selectivity and less adverse effects than inhibitors, indicating that PROTACs had a great potential for overcoming clinical drug resistance and safety issues. [Read the Full Post]

Lenvatinib and Sorafenib for Differentiated Thyroid Cancer After Radioactive Iodine: A Systematic Review and Economic Evaluation

610 | Jul 13 2020

Nigel Fleeman et al.showed that compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. [Read the Full Post]

Discovery of Novel Dual c-Met/HDAC Inhibitors as a Promising Strategy for Cancer Therapy

609 | Jul 07 2020

Hao Hu et al. provided an efficient strategy for discovery of multitarget antitumor drugs. [Read the Full Post]

Efficacy of Gefitinib Combined With 125 I Radioactive Particles in the Treatment of Transplanted Lung Cancer Tumors in Nude Mice

663 | Jul 02 2020

Chaojie Li et al. found that Gefitinib combined with 125I radioactive particles brachytherapy could significantly inhibit tumor growth. [Read the Full Post]

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

788 | Jun 19 2020

James Chih-Hsin Yang et al. found that Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutatios. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings. [Read the Full Post]

STMN1 Upregulation Mediates Hepatocellular Carcinoma and Hepatic Stellate Cell Crosstalk to Aggravate Cancer by Triggering the MET Pathway

644 | Jun 15 2020

Rui Zhang et al. suggested that STMN1 may be used as a potential marker to identify patients who may benefit from MET inhibitor treatment. [Read the Full Post]

Real-World Treatment Patterns and Progression-Free Survival Associated With Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non-Small Cell Lung Cancer

469 | Jun 08 2020

Mohammad Jahanzeb et al. found that median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for first- and second-line ALK TKI therapy and was even shorter in patients with brain metastasis, highlighting the need for more effective treatments in this patient population. [Read the Full Post]

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

829 | Jun 05 2020

Marco Malavolta et al. explored the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, migtht drive the deleterious consequences of the infection. [Read the Full Post]

A Natural Anthraquinone Derivative Shikonin Synergizes With AZD9291 Against wtEGFR NSCLC Cells Through Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress

494 | Jun 01 2020

Xiu Hu et al. suggested that combining shikonin with AZD9291was a promising therapeutic strategy for treating wtEGFR NSCLC patients. [Read the Full Post]

Essential Thrombocythemia Treatment Algorithm 2018

741 | May 24 2020

Ayalew Tefferi et al. provided a point-of-care treatment algorithm that was risk-adapted and based on evidence and decades of experience. [Read the Full Post]

Effects of PCI-32765 and Dasatinib on the Acute Lymphoblastic Leukemic Cells and Their Mechanisms

616 | May 20 2020

Yuan Deng et al. found that PCI-32765 or Dasatinib could inhibit the proliferation and induced the apoptosis of Sup-B15 and RS4;11 cells, PCI-32765 and Dasatinib displayed the synergistic effects. The possible mechanismmight be related with the blocking of B cell receptor(BCR) signal pathway, thereby inhibiting the cell proliferation and promoting the cell apoptosis. [Read the Full Post]

Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in CLL

499 | May 17 2020

Rendeiro AF et al. described time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL [Read the Full Post]

Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha

569 | May 10 2020

Koh MY et al. concluded that PX-478 inhibits HIF-1alpha at multiple levels that together or individually may contribute to its antitumor activity against HIF-1alpha-expressing tumors. [Read the Full Post]

anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells

400 | May 10 2020

Liu S et al. demonstrated that PD-L1 high expression on VECs inhibits the infiltration of CD8+ T cells, whereas promotes the aggregation of FoxP3+ T cells into tumor tissues, thus becoming an "immunosuppressive barrier". Anlotinib can ameliorate the immuno-microenvironment by downregulating PD-L1 expression on VECs to inhibit tumor growth. [Read the Full Post]

A novel flow cytometry-based assay to measure compromised B cell receptor signaling as a prognostic factor in chronic lymphocytic leukemia

486 | May 06 2020

Heitmann JS et al. supported the role of compromised BCR signaling as an important prognostic marker in CLL and establish a novel diagnostic tool for its assessment in clinical settings. [Read the Full Post]

YH25448, an Irreversible EGFR-TKI With Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

1090 | Apr 23 2020

Jiyeon Yun et al. suggested that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Design, Synthesis and Biological Evaluation of 2-amino-4-(1,2,4-triazol)pyridine Derivatives as Potent EGFR Inhibitors to Overcome TKI-resistance

512 | Apr 22 2020

Haikui Yang et al. provided 2-amino-4-(1,2,4-triazol)pyridines as a new scaffold for EGFRT790M and/or EGFRvⅢ inhibitor. [Read the Full Post]

The Syk Inhibitor R406 Is a Modulator of P-glycoprotein (ABCB1)-mediated Multidrug Resistance

513 | Apr 21 2020

George E Duran et al. indicated that the chemo-sensitizing effect of R406 in taxane-resistant cells previously reported was not associated with Syk but resulted from the modulation of P-gp-mediated MDR. [Read the Full Post]

Attenuated isolated 3' signal: A highly challenging therapy relevant ALK FISH pattern in NSCLC

445 | Apr 11 2020

Smuk G et al. indicated the adequate therapy with higher efficiency for patients suffering from NSCLC. [Read the Full Post]

Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis

551 | Apr 10 2020

Shah N et al. demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment. [Read the Full Post]

Sphingosine Kinase 1 in Breast Cancer-A New Molecular Marker and a Therapy Target

586 | Apr 09 2020

Alshaker H et al. concluded that SK1 may have a potential as a target for precision medicine, its high expression being a negative prognostic marker in ER-negative breast cancer, as well as a target for chemosensitization therapy. [Read the Full Post]

NTRK fusion-positive cancers and TRK inhibitor therapy

0 | Apr 05 2020

Cocco E D et al. discussed the biology of NTRK fusions, strategies to target these drivers in the treatment-naive and acquired-resistance disease settings, and the unique safety profile of TRK inhibitors. [Read the Full Post]

Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells

0 | Apr 01 2020

Cervantes-Madrid D et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study

535 | Mar 29 2020

Li Y et al. indicated that TLC demonstrated promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice. [Read the Full Post]

Glucocorticoid resistance is reverted by LCK inhibition in pediatric T-cell acute lymphoblastic leukemia

614 | Mar 24 2020

Serafin V et al. suggested a quickly actionable approach to supporting conventional therapies and overcoming GC resistance in pediatric T-ALL patients. [Read the Full Post]

NTRK fusion-positive cancers and TRK inhibitor therapy

812 | Mar 23 2020

Cocco E et al. discussed the biology of NTRK fusions, strategies to target these drivers in the treatment-naive and acquired-resistance disease settings, and the unique safety profile of TRK inhibitors. [Read the Full Post]

The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice

417 | Mar 21 2020

Parikh SA et al. illustrated the challenges associated with continuous oral therapy with ibrutinib in patients with CLL. [Read the Full Post]

Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in CLL

525 | Mar 21 2020

Rendeiro AF et al. described time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1044 | Mar 14 2020

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

Molecular alterations and poziotinib efficacy, a pan-HER inhibitor, in human epidermal growth factor receptor 2 (HER2)-positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2-positive breast cancer patients

513 | Mar 11 2020

Koga T et al. identified HER2 CN amplification, PIK3CA pathway alteration, and ERBB3 cytoplasmic mutation showed predictive roles on clinical outcomes of HER2-positive MBC treated with poziotinib. [Read the Full Post]

Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study

609 | Mar 10 2020

Koga T et al. identified the secondary C805S at the covalent binding site of HER2 to poziotinib as a potential mechanism of acquired resistance. HSP90 inhibitors might be a therapeutic strategy for the C805S secondary mutation. [Read the Full Post]

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis

918 | Mar 09 2020

Torres-Hernandez A et al. suggested that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis. [Read the Full Post]

Simultaneous inhibition of JAK and SYK kinases ameliorates chronic and destructive arthritis in mice

434 | Mar 08 2020

Llop-Guevara A et al. showed that concurrent JAK + SYK inhibition resulted in higher efficacy than single kinase inhibition and TNF blockade in a chronic and severe arthritis model. Thus, blockade of multiple immune signals with dual JAK + SYK inhibition represents a reasonable therapeutic strategy for RA, in particular in patients with inadequate responses to current treatments. Our data supports the multiplicity of events underlying this heterogeneous and complex disease. [Read the Full Post]

Phase I Dose-Escalation Study of the pan-HER Inhibitor, PF299804, in Patients With Advanced Malignant Solid Tumors

538 | Mar 02 2020

Pasi A Jänne et al. showed the MTD of PF299804 is 45 mg/d. Both continuous and intermittent treatment schedules were well tolerated, and encouraging signs of antitumor activity were observed in gefitinib/erlotinib treated NSCLC patients. [Read the Full Post]

The Syk Inhibitor Fostamatinib Disodium (R788) Inhibits Tumor Growth in the Eμ- TCL1 Transgenic Mouse Model of CLL by Blocking Antigen-Dependent B-cell Receptor Signaling

723 | Feb 26 2020

Mirza Suljagic et al. provided further rationale for clinical trials with R788 in CLL and establish the BCR-signaling pathway as an important therapeutic target in this disease. [Read the Full Post]

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

537 | Feb 25 2020

McDermott DF et al. suggested that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade. [Read the Full Post]

Repotrectinib (TPX-0005), Effectively Reduces Growth of ALK Driven Neuroblastoma Cells

1400 | Feb 19 2020

Diana Cervantes-Madrid et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Repotrectinib (TPX-0005), Effectively Reduces Growth of ALK Driven Neuroblastoma Cells

0 | Feb 19 2020

Diana Cervantes-Madrid et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Administration of Lapatinib with Food Increases Its Plasma Concentration in Chinese Patients with Metastatic Breast Cancer: A Prospective Phase II Study

592 | Feb 16 2020

Xu F et al. showed that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug-related toxicity. We suggest that a larger-sample-size clinical trial is needed to fully understand the effect of administration of lapatinib with food. [Read the Full Post]

The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells

722 | Feb 12 2020

Jiang X et al. proposed that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein. [Read the Full Post]

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

885 | Feb 07 2020

Casavecchia G et al. reported and discussed most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. [Read the Full Post]

CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant

472 | Feb 04 2020

Sakamoto H et al. supported the potential for clinical evaluation of CH5424802 for the treatment of patients with ALK-driven tumors. [Read the Full Post]

Protein tyrosine kinase 2: a novel therapeutic target to overcome acquired EGFR-TKI resistance in non-small cell lung cancer

584 | Feb 03 2020

Tong X et al. suggested that this combination therapy may be a viable option to overcome EGFR-TKI resistance in NSCLC. [Read the Full Post]

Treatment outcome and clinical characteristics of HER2 mutated advanced non-small cell lung cancer patients in China

584 | Feb 01 2020

Fei Xu et al. found that HER2 mutated lung cancer patients were younger, mostly females, never or light smokers, with histologically diagnosed adenocarcinomas. Compared with afatinib, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype. [Read the Full Post]

Determination of Somatic Mutations and Tumor Mutation Burden in Plasma by CAPP-Seq during Afatinib Treatment in NSCLC Patients Resistance to Osimertinib

712 | Feb 01 2020

Ishii H et al. demonstrated that detection of mutant allele frequency and TMB of ctDNA by CAPP-Seq could help determine the effectiveness of and resistance to afatinib. [Read the Full Post]

Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)

570 | Jan 25 2020

Yang PW et al. demonstrated that both cabozantinib and R428 inhibit ESCC growth in cell and xenograft models. The results reveal the great potential of using cabozantinib for targeted therapy of ESCC. [Read the Full Post]

Non-Photoinduced Biological Properties of Verteporfin

0 | Jan 23 2020

Gibault F et al. indicated that VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD. [Read the Full Post]

Molecular therapies and precision medicine for hepatocellular carcinoma

571 | Jan 23 2020

Llovet JM et al. summarized the molecular targets and therapies for the management of HCC and discuss the advancements expected in the near future, including biomarker-driven treatments and immunotherapies. [Read the Full Post]

CAR T-cells targeting FLT3 have potent activity against FLT3-ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib

0 | Jan 22 2020

Jetani H et al. provided the first proof-of-concept that CAR T-cell immunotherapy and small molecule inhibition can be used synergistically, as exemplified by our data showing superior antileukemia efficacy of FLT3-CAR T-cells in combination with crenolanib. [Read the Full Post]

Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury

623 | Jan 01 2020

Yang Y et al. indicated that FG-4592 treatment remarkably ameliorated the cisplatin-induced kidney injury possibly through the stabilization of HIF. Thus, besides the role in treating CKD anemia, the clinical use of FG-4592 also could be extended to AKI. [Read the Full Post]

Identification of RNPC3 as a novel JAK2 fusion partner gene in B-acute lymphoblastic leukemia refractory to combination therapy including ruxolitinib

712 | Dec 31 2019

Chen X et al. suggested the potential need for a diagnostic FISH analysis as well as RNA-Seq in the appropriate clinical setting. [Read the Full Post]

Characteristics of Patients With ROS1+ Cancers: Results From the First Patient-Designed, Global, Pan-Cancer ROS1 Data Repository

999 | Dec 30 2019

This study is the first global, patient-designed approach, to our knowledge, to comprehensively assess demographic, clinical, and environmental characteristics associated with ROS1+ cancers. [Read the Full Post]

Highly accurate DNA-based detection and treatment results of MET exon 14 skipping mutations in lung cancer

922 | Dec 27 2019

Pruis MA et al. showed that METex14del can be reliably detected by routine DNA NGS analysis. [Read the Full Post]

The development of HKI-272 and related compounds for the treatment of cancer

668 | Dec 22 2019

Wissner A et al. highlight the findings that these irreversible inhibitors retain activity against tumors that have acquired a resistance to the reversible binding inhibitors gefitinib and erlotinib. The promising interim clinical trial results for HKI-272 and EKB-569 in treating colon, lung, and breast cancers are summarized. [Read the Full Post]

miR-193b-Regulated Signaling Networks Serve as Tumor Suppressors in Liposarcoma and Promote Adipogenesis in Adipose-Derived Stem Cells

564 | Dec 16 2019

Mazzu YZ et al. indicated that miR-193b not only functions as a tumor suppressor in liposarcoma but also promotes adipogenesis in ASC. Furthermore, this study reveals key tyrosine kinase and DNA methylation pathways in liposarcoma, some with immediate implications for therapeutic exploration. [Read the Full Post]

Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in vivo studies

0 | Dec 14 2019

Li J et al. demonstrated that quizartinib potentiates the antineoplastic activity of wild-type and R482T mutant ABCG2 substrates. These findings may be useful in clinical practice for cancer combination therapy with quizartinib. [Read the Full Post]

A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification

0 | Dec 14 2019

Van Cutsem E et al. showed that AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated. [Read the Full Post]

Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells

958 | Dec 10 2019

Kuntz EM et al. provided a strong rationale for investigation of the use of TKIs in combination with tigecycline to treat patients with CML with minimal residual disease. [Read the Full Post]

Efficacy of BIBF 1120 or BIBF 1120 plus chemotherapy on nasopharyngeal carcinoma in vitro and in vivo

0 | Dec 03 2019

Xue C et al. indicated that BIBF 1120 administered in conjunction with chemotherapy might provide an effective treatment method for NPC. [Read the Full Post]

A Genome-Wide CRISPR Screen Identifies Genes Critical for Resistance to FLT3 Inhibitor AC220

0 | Nov 19 2019

Hou P et al. identified novel genes whose loss of function conferred resistance to a selective FLT3 inhibitor, providing new insight into signaling pathways that contribute to acquired resistance in AML. [Read the Full Post]

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

476 | Nov 18 2019

McGivern N et al. provided a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials. [Read the Full Post]

PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines

491 | Nov 17 2019

Nakachi I et al. indicated PTTG1 may be a valuable biomarker in ovarian cancer to predict sensitivity to saracatinib, and could form the basis of a targeted prospective saracatinib trial for ovarian cancer. [Read the Full Post]

Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials

464 | Nov 04 2019

Zhou Y et al. aimed to compare the adverse drug events which were associated with the use of ibrutinib for the treatment of patients with CLL. [Read the Full Post]

Itraconazole increases ibrutinib exposure ten-fold and reduces inter-individual variation - A potentially beneficial drug-drug interaction

489 | Nov 03 2019

Tapaninen T et al. found that itraconazole markedly increases ibrutinib bioavailability and decreases its inter-individual variability, offering a possibility to improved dosing accuracy and cost savings. [Read the Full Post]

The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models

690 | Nov 02 2019

Zhang S et al. provided the molecular basis for the promising activity being observed in ALK+, crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. [Read the Full Post]

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model

524 | Oct 18 2019

Komla-Ebri D et al. demonstrated that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH. [Read the Full Post]

Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC

870 | Oct 18 2019

Wei L et al. demonstrated that targeting PHGDH is an effective approach to overcome TKI drug resistance in HCC. [Read the Full Post]

Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma

700 | Oct 17 2019

Javle M et al. indicated that BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population. [Read the Full Post]

Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors

632 | Oct 16 2019

Nishio M et al. indicated that ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing. [Read the Full Post]

Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis

711 | Oct 15 2019

Ruprecht B et al. offered deeper perspectives on cancer drug resistance and suggests new biomarkers and treatment options for lapatinib-resistant cancers. [Read the Full Post]

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

834 | Oct 09 2019

Sandborn WJ et al. showed that in patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

701 | Oct 09 2019

Li F et al. demonstrated a significant merit of our method in the identification of the bioactive compounds in natural products. [Read the Full Post]

BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

789 | Oct 05 2019

Li D et al. showed that BIBW2992, an anilino-quinazoline designed to irreversibly bind EGFR and HER2, potently suppresses the kinase activity of wild-type and activated EGFR and HER2 mutants, including erlotinib-resistant isoforms. Consistent with this activity, BIBW2992 suppresses transformation in isogenic cell-based assays, inhibits survival of cancer cell lines and induces tumor regression in xenograft and transgenic lung cancer models, with superior activity over erlotinib. These findings encourage further testing of BIBW2992 in lung cancer patients harboring EGFR or HER2 oncogenes. [Read the Full Post]

Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models

1085 | Sep 23 2019

Gozgit JM et al. showed that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers. [Read the Full Post]

E7080 (lenvatinib), a multi-targeted tyrosine kinase inhibitor, demonstrates antitumor activities against colorectal cancer xenografts

0 | Sep 22 2019

Wiegering A et al. suggested antiangiogenic activity of E7080 at a dosage that was well tolerated by nude mice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS. [Read the Full Post]

Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth

568 | Sep 15 2019

Yakes FM et al. suggested that cabozantinib is a promising agent for inhibiting tumor angiogenesis and metastasis in cancers with dysregulated MET and VEGFR signaling. [Read the Full Post]

Effective combinatorial immunotherapy for castration-resistant prostate cancer

0 | Sep 15 2019

Lu X et al. illuminated a clinical path hypothesis for combining immune checkpoint blockade with MDSC-targeted therapies in the treatment of mCRPC. [Read the Full Post]

ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy

658 | Sep 03 2019

Wakeling AE et al. indicated the potential utility of ZD1839 in the treatment of many human tumors and indicate that continuous once-a-day p.o. dosing might be a suitable therapeutic regimen. [Read the Full Post]

Brief Report: Rapid Acquisition of Alectinib Resistance in ALK-positive Lung Cancer with High Tumor Mutation Burden

532 | Aug 16 2019

Makimoto G et al. found that high TMB and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. [Read the Full Post]

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

759 | Aug 15 2019

Noronha V et al. found that adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC. [Read the Full Post]

Yiqi Chutan Tang Reduces Gefitinib-Induced Drug Resistance in Non-Small-Cell Lung Cancer by Targeting Apoptosis and Autophagy

646 | Aug 15 2019

Zhang J et al. provided a new treatment strategy for patients with EGFR-TKI resistance in NSCLC. [Read the Full Post]

Treatment Patterns in Patients with Chronic-Phase Chronic Myeloid Leukaemia in Routine Clinical Practice: the SIMPLICITY Italian Population

1411 | Aug 10 2019

Abruzzese E et al. provided valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice. [Read the Full Post]

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

979 | Aug 07 2019

Verstovsek S et al. indicated that INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed. [Read the Full Post]

PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations

1086 | Aug 05 2019

Zou HY et al. indicated that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation. [Read the Full Post]

Overcoming Acquired Resistance to AZD9291, A Third-Generation EGFR Inhibitor, through Modulation of MEK/ERK-Dependent Bim and Mcl-1 Degradation

629 | Jul 25 2019

Shi P et al. showed that modulation of MEK/ERK-dependent Bim and Mcl-1 degradation critically mediates sensitivity and resistance of EGFR-mutant NSCLC cells to AZD9291 and hence is an effective strategy to overcome acquired resistance to AZD9291. [Read the Full Post]

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

554 | Jul 16 2019

Honigberg LA et al. support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway. [Read the Full Post]

JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation

884 | Jul 08 2019

Lu Z et al. justified further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies. [Read the Full Post]

Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study

667 | Jul 07 2019

Fennell DA et al. indicated that neither PFS nor OS was improved by defactinib after first-line chemotherapy in patients with merlin-low MPM. Defactinibcannot be recommended as maintenance therapy for advanced MPM. [Read the Full Post]

A high-performance liquid chromatography-tandem mass spectrometry method for the determination of lifrafenib, a novel RAF kinase and EGFR inhibitor, in human plasma and urine and its application in clinical pharmacokinetic study

714 | Jul 01 2019

Yao X et al. showed robust and sensitive, it successfully fulfilled the requirement of clinical pharmacokinetic study of lifirafenib in Chinese patients with locally advanced or metastatic solid tumors. [Read the Full Post]

Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects

819 | Jun 30 2019

Tran P et al. presented the results of human oral absorption, distribution, metabolism, excretion (ADME) and in vitro studies that together provide an overall understanding of the metabolism, distribution and clearance of asciminib in humans. [Read the Full Post]

Fibroblast Growth Factor Receptor 4 Targeting in Cancer: New Insights into Mechanisms and Therapeutic Strategies

637 | Jun 28 2019

Lang L et al. indicated their aim is to pinpoint the potential of FGFR4 as a therapeutic target and identify new avenues for advancing future research in the field. [Read the Full Post]

TKI-Related Platelet Dysfunction Does Not Correlate With Bleeding in Patients With Chronic Phase-Chronic Myeloid Leukemia With Complete Hematological Response

901 | Jun 21 2019

Sener Y et al. concluded that TKIs may impair in vitro platelet aggregation but this impairment is not associated with bleeding diathesis. [Read the Full Post]

Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells

847 | Jun 18 2019

Huang F et al. indicated the potential of repositioning afatinib or other ERBB-family-targeted agents for improving radiation response in NPC cells. [Read the Full Post]

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase

887 | Jun 12 2019

Huang WS et al. showed that brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial. [Read the Full Post]

NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors

788 | Jun 08 2019

Park HR et al. suggested that combinational treatment with NK cell-based immunotherapy and cetuximab may be promising for patients with TKI-resistant NSCLC. [Read the Full Post]

ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial

1001 | Jun 02 2019

Gorcea CM et al. showed that ASP2215 (gilteritinib) is a novel, dual FLT3/AXL inhibitor with promising early phase trial data (NCT02014558). [Read the Full Post]

Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial

814 | May 07 2019

Shaw AT et al. indicated lorlatinib might be an effective therapeutic strategy for patients with ALK-positive NSCLC who have become resistant to currently available TKIs, including second-generation ALK TKIs, and is being investigated in a phase 3 randomised controlled trial comparing lorlatinib to crizotinib (ClinicalTrials.gov, NCT03052608). [Read the Full Post]

Thromboembolic events in polycythemia vera

1070 | Apr 27 2019

Griesshammer M et al. discussed factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV. [Read the Full Post]

Mechanisms of Action of Ruxolitinib in Murine Models of Hemophagocytic Lymphohistiocytosis

1184 | Apr 26 2019

Ruxolitinib operates through IFNγ-dependent and independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis. [Read the Full Post]

Favorable predictors for survival in advanced ALK-positive non-small cell lung cancer patients beyond crizotinib resistance

642 | Apr 24 2019

Xu H et al. found that long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next-generation ALK inhibitors might be favorable predictors for OS in advanced ALK-positive NSCLC patients. [Read the Full Post]

High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma

702 | Apr 14 2019

Wang S et al. indicated that FAK and Aurora kinase B inhibitors synergistically impair Ewing sarcoma cell viability and significantly inhibit tumor progression. This study provides preclinical support for the consideration of a clinical trial testing the safety and efficacy of this combination for patients with Ewing sarcoma. [Read the Full Post]

lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling

0 | Apr 10 2019

Lu Y et al. described a double-negative feedback loop between MIR100HG and the transcription factor GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR-125b targeting of GATA6. These findings identify a clinically actionable, epigenetic cause of cetuximab resistance. [Read the Full Post]

Roxadustat in the treatment of anaemia in chronic kidney disease

795 | Mar 31 2019

Del Vecchio L et al showed that Roxadustat is a chemical drug and thus has the potential of being cheaper than traditional ESAs. Given that the peaks of endogenous EPO are much lower than those observed with traditional ESA, it is possible to speculate the roxadustat (and more in general PHD inhibitors) will be safer than ESA on cardiovascular safety end-points. Considering that HIFs are involved in different pathways, with possible promotion of relevant side effects, their safety must be proven in long-term studies. [Read the Full Post]

Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China

780 | Mar 31 2019

Chen N et al. showed that FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program. [Read the Full Post]

Ibrutinib for the treatment of chronic lymphocytic leukemia

684 | Mar 30 2019

Novel, extremely promising, combination strategies, based on the association of ibrutinib with chemoimmunotherapy, antiCD20 monoclonal antibody or other targeted agents, are currently being investigated, with the goal of achieving greater depth of remission, especially MRD-negativity, and removing the need for indefinite treatment. [Read the Full Post]

Lenvatinib versus placebo in radioiodine-refractory thyroid cancer

794 | Mar 25 2019

Schlumberger M et al. indicated that Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. [Read the Full Post]

E7080 (lenvatinib), a multi-targeted tyrosine kinase inhibitor, demonstrates antitumor activities against colorectal cancer xenografts

667 | Mar 25 2019

Wiegering A et al. suggested antiangiogenic activity of E7080 at a dosage that was well tolerated by nude mice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS. [Read the Full Post]

Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials

842 | Mar 20 2019

Tao Z et al. demonstrated that neratinib provides a benefit in survival outcome. When combined with other anticancer agents, neratinib may hold promise for treating breast cancer with central nervous system metastases. [Read the Full Post]

Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

1055 | Mar 19 2019

Martin M et al. showed that at the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events. [Read the Full Post]

A Genome-Wide CRISPR Screen Identifies Genes Critical for Resistance to FLT3 Inhibitor AC220

780 | Mar 07 2019

Hou P et al. identified novel genes whose loss of function conferred resistance to a selective FLT3 inhibitor, providing new insight into signaling pathways that contribute to acquired resistance in AML. [Read the Full Post]

Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in vivo studies

716 | Mar 05 2019

Li J et al. demonstrated that quizartinib potentiates the antineoplastic activity of wild-type and R482T mutant ABCG2 substrates. These findings may be useful in clinical practice for cancer combination therapy with quizartinib. [Read the Full Post]

Risk of anastomotic dehiscence in patients with pulmonary fibrosis transplanted while receiving anti-fibrotics: Experience of the Australian Lung Transplant Collaborative

801 | Mar 04 2019

Mackintosh JA et al. showed the incidence of bronchial dehiscence after transplantation for IPF is low and is not significantly higher in patients receiving anti-fibrotic therapy at the time of transplantation. [Read the Full Post]

Efficacy of BIBF 1120 or BIBF 1120 plus chemotherapy on nasopharyngeal carcinoma in vitro and in vivo

912 | Mar 04 2019

Xue C et al. indicated that BIBF 1120 administered in conjunction with chemotherapy might provide an effective treatment method for NPC. [Read the Full Post]

Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds

2839 | Feb 24 2019

Abdelhafez OM et al. indicated these promising results of cytotoxic activity and significant inhibition of p38α MAP kinase, were confirmed by exploring the effect of benzofuran derivative (18) on the apoptotic induction and cell cycle progression of MCF-7 cell line. Compound 18 induced preG1 apoptosis and cell growth arrest at G2/M phase preventing the mitotic cycle. Moreover it activated the caspase-7 which executes apoptosis. Molecular docking study was carried out using GOLD program to predict the mode of binding interaction of the synthesized compounds into the target p38α MAPK. Additionally, the physicochemical properties and ADME parameters of compound 18 were examined in silico to investigate its drug-likeness. [Read the Full Post]

Crenolanib is a selective type I pan-FLT3 inhibitor

673 | Feb 21 2019

Smith CC et al. showed that Crenolanib has significant promise for achieving deep and durable responses in FLT3-mutant AML, and may have a profound impact upon future medicinal chemistry efforts in oncology. [Read the Full Post]

Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the Regorafenib in Metastatic colorectal cancer - An Indian exploratory analysis study

900 | Feb 19 2019

Ramaswamy A et al. indicated duration of treatment with regorafenib as an efficacy end point in this study is similar to available data from other regions as it is the side effect profile. [Read the Full Post]

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial

1136 | Feb 18 2019

Bruix J et al. indicated that regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib. [Read the Full Post]

Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility

0 | Feb 10 2019

Fujimoto T et al. suggested that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2. [Read the Full Post]

Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma

829 | Feb 07 2019

Martin MJ et al. supported a model in which the combination of osimertinib and OxPhos inhibitors can delay or prevent resistance in osimertinib-naïve tumour cells, and represents a novel strategy that warrants further pre-clinical investigation. [Read the Full Post]

Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium

670 | Feb 06 2019

Huang J et al. identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

1455 | Jan 22 2019

Suttorp M et al. indicated that adherence to imatinib intake may be the most prominent factor influencing treatment outcome in teenagers thus pointing towards the potential benefits of regular drug monitoring. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

0 | Jan 22 2019

Suttorp M et al. indicated taht pharmacokinetic variables (e.g. alpha 1-acid glycoprotein binding, drug-drug/food-drug interactions via cytochrome P450 3A4/5, cellular uptake mediated via OCT-1-influx variations and P-glycoprotein-mediated drug efflux) still await to be addressed in pediatric patients systematically. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Jan 19 2019

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification

967 | Jan 15 2019

Van Cutsem E et at. indicated that AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated. [Read the Full Post]

The thrombopoietin/MPL axis is activated in the Gata1low mouse model of myelofibrosis and is associated with a defective RPS14 signature

1264 | Dec 30 2018

Zingariello M et al. showed that Gata1low mice are a bona fide model of MF, which recapitulates the hyperactivation of the TPO/MPL/JAK2 axis observed in megakaryocytes from myelofibrotic patients. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

0 | Dec 30 2018

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells

1328 | Nov 28 2018

Li MZ et al. indicated that SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

5972 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

0 | Nov 20 2018

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo

1965 | Nov 19 2018

Zhu Y et al. indicated that PX-478 had significant antitumor activity against HIF-1α over-expressing ESCC tumors in vitro and in vivo. These results opened up the possibility of inhibiting HIF-1α for targeted therapy of ESCC. [Read the Full Post]

Regulation of angiogenic behaviors by oxytocin receptor through Gli1-indcued transcription of HIF-1α in human umbilical vein endothelial cells

1954 | Nov 19 2018

Zhu J et al. suggested that oxytocin receptor signaling promoted the angiogenic behaviors of HUVECs via Gli1-indcued transcription of HIF-1α. We provided novel molecular insights into endothelial cell-mediated angiogenesis. [Read the Full Post]

The Aryl Hydrocarbon Receptor Governs Epithelial Cell Invasion during Oropharyngeal Candidiasis

758 | Nov 16 2018

Solis NV et al. indicated that AhR plays a central role in governing the pathogenic interactions of C. albicans with oral epithelial cells during OPC and suggested that this receptor is a potential therapeutic target [Read the Full Post]

JAK2 inhibitor CEP-33779 prevents mouse oocyte maturation in vitro

1204 | Nov 15 2018

Wu C et al. suggested that JAK2 regulated the microfilaments aggregation during the mouse oocyte maturation. [Read the Full Post]

The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro

1403 | Nov 13 2018

Shiomitsu K et al. suggested the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy. [Read the Full Post]

Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants

1934 | Nov 11 2018

Lee S et al indicated that sclareol attenuated UVB-induced photo-aging by an increase in collagen synthesis and decrease in MMP-1 activity. [Read the Full Post]

Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism

995 | Nov 07 2018

Feng X et al. illustrated that caspase 3 activation in dying glioma cells unfavorably supported post-irradiation angiogenesis. This double-edged role of caspase 3 suggested that taming caspase 3 from the opposite side, not always activating it, may provide novel therapeutic strategies due to restricted post-irradiation angiogenesis. [Read the Full Post]

The afatinib resistance of in vivo generated H1975 lung cancer cell clones is mediated by SRC/ERBB3/c-KIT/c-MET compensatory survival signaling

0 | Nov 07 2018

Booth L et al. indicated that inhibition of ERBB3 signaling via both blockade of SRC and ERBB1 results in tumor cell death. [Read the Full Post]

Pro-survival signal inhibition by CDK inhibitor dinaciclib in Chronic Lymphocytic Leukaemia

0 | Nov 06 2018

Chen Y et al. showed that dinaciclib targets multiple pro-survival signalling pathways in CLL, which provides a mechanistic explanation for its potent induction of apoptosis. They also support a therapeutic application of cyclin-dependent kinase inhibitors in CLL in combination with other relevant targeted therapies. [Read the Full Post]

Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility

1025 | Nov 06 2018

Fujimoto T et al. suggested that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2. [Read the Full Post]

No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

0 | Nov 04 2018

Peterse EF et al. indicated that the IGF pathway is not essential for chondrosarcoma growth, migration or chemoresistance. Furthermore, IGF1R is only minimally expressed in chondrosarcoma primary tumours. Therefore, the IGF pathway is not expected to be an effective therapeutic target for chondrosarcoma of bone. [Read the Full Post]

Steroid hormone 20-hydroxyecdysone promotes higher calcium mobilization to induce apoptosis

871 | Oct 31 2018

Wang D et al. suggested that 20E and JH via different pathways regulate calcium mobilization and homeostasis at different levels, thus inform different gene expression and cellular responses. [Read the Full Post]

Relaxing Effect of TSU-68, an Antiangiogenic Agent, on Mouse Airway Smooth Muscle

732 | Oct 30 2018

Tan H et al. indicated that TSU-68 relaxes tense ASM by reducing the intracellular Ca2+ concentration through blocking VDCCs and NSCCs, which suggested that this small molecule might be useful in the treatment of abnormal smooth muscle. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

0 | Oct 25 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells

973 | Oct 25 2018

Ramirez M et al. found that the drug-tolerant persister state does not limit--and may even provide a latent reservoir of cells for--the emergence of heterogeneous drug-resistance mechanisms. [Read the Full Post]

Three-dimensional biomimetic model to reconstitute sprouting lymphangiogenesis in vitro

720 | Oct 23 2018

Kim S et al. not only revealed critical but unappreciated role of mechanical cue that regulates lymphangiogenic sprouting, but also provides a novel biomimetic model that may leverage further biological studies as well as phenotypic drug screening. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

1622 | Oct 20 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

PDE5 inhibitors enhance the lethality of [pemetrexed + sorafenib]

1210 | Oct 19 2018

Booth L et al. argued that additional clinical studies combining pemetrexed, sorafenib and sildenafil are warranted. [Read the Full Post]

Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization.

888 | Oct 18 2018

Guo H et al. proposed that the secreted AGR2 is a blockable molecular target, which acts as a chaperon-like enhancer to VEGF and FGF2. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | Oct 14 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1793 | Oct 12 2018

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system

908 | Oct 08 2018

Jiang Y et al. demonstrated that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC-mediated paracrine effect of VEGF on BMSCs. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Oct 01 2018

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. [Read the Full Post]

Efficient extravasation of tumor-repopulating cells depends on cell deformability

769 | Sep 30 2018

Chen J et al. suggested that tumor cell deformability is a key factor in controlling extravasation dynamics during metastasis. [Read the Full Post]

Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties

704 | Sep 28 2018

Les F et al.found that piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it. [Read the Full Post]

Efficacy of focal adhesion kinase inhibition in non-small cell lung cancer with oncogenically activated MAPK pathways

1016 | Sep 27 2018

Zhang H, et al. demonstrated efficacy both in vitro and in vivo in lung cancers with either oncogenic RAS or EGFR mutations. In addition, FAK inhibition in combination with inhibitors of Bcl-2 family of anti-apoptotic proteins has synergistic activity in these MAPK-activated non-small cell lung cancer cell line models. [Read the Full Post]

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent

886 | Sep 27 2018

Batista de Carvalho AL et al. aimed at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials. [Read the Full Post]

Inhibition of adhesion, migration and of α5β1 integrin in the HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A

2628 | Sep 26 2018

Pelillo C et al. supported the new concept that metal-based drugs can inhibit tumour metastases through targeting of integrins and of other proteins which mediate tumour progression-related cell functions such as adhesion and migration. [Read the Full Post]

Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors

1358 | Sep 07 2018

Gunerka P et al. suggested that observed effect of JAK2 inhibitors on transcription and cell cycle level in different cell lines are associated not with activity within JAK family, but presumably with other off-target activities. [Read the Full Post]

Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis

1555 | Aug 22 2018

Hang L et al. indicated that downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis. [Read the Full Post]

FYN promotes breast cancer progression through epithelial-mesenchymal transition

0 | Aug 20 2018

Xie YG et al. found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. [Read the Full Post]

The cKit Inhibitor, Masitinib, Prevents Diabetes-Induced Retinal Vascular Leakage

1008 | Aug 10 2018

Kim SR et al. provided the first demonstration that cKit inhibitors, such as masitinib, might be promising therapeutics for prevention of diabetes-induced breakdown of the BRB. [Read the Full Post]

Local release of masitinib alters in vivo implantable continuous glucose sensor performance

889 | Aug 09 2018

Avula M et al. showed that the mast cell-targeting tyrosine kinase inhibitor, masitinib, was released from degradable polymer microspheres delivered from the surfaces of FDA-approved human commercial CGM needle-type implanted sensors in a rodent subcutaneous test bed. By targeting the mast cell c-Kit receptor and inhibiting mast cell activation and degranulation, local masitinib penetration around the CGM to several hundred microns sought to reduce sensor fibrosis to extend CGM functional lifetimes in subcutaneous sites. Drug-releasing and control CGM implants were compared in murine percutaneous implant sites for 21 days using direct-wire continuous glucose reporting. Drug-releasing implants exhibited no significant difference in CGM fibrosis at implant sites but showed relatively stable continuous sensor responses over the study period compared to blank microsphere control CGM implants. [Read the Full Post]

Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis

0 | Aug 09 2018

Sun X et al. showed that metallothionein (MT)-1G is a critical regulator and promising therapeutic target of sorafenib resistance in human HCC cells. [Read the Full Post]

JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

1174 | Aug 02 2018

Gao SP et al. revealed a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC. [Read the Full Post]

Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

1372 | Aug 01 2018

Park JH et al. suggested that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. [Read the Full Post]

A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation

1075 | Jul 20 2018

Grassilli E et al. revealed that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach. [Read the Full Post]

BTK inhibition is a potent approach to block IgE-mediated histamine release in human basophils

1038 | Jul 19 2018

Smiljkovic D et al. indicated that BTK-targeting drugs are potent inhibitors of IgE-dependent histamine release in human basophils. The clinical value of BTK inhibition in the context of allergic diseases remains to be determined. [Read the Full Post]

B7-H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin-6/signal transducer and activator of transcription 3 pathway activation

1606 | Jul 13 2018

Chen X et al. provided the first evidence that B7-H4 facilitated ESCC cell proliferation through promoting IL-6/STAT3 positive loopback pathway activation. [Read the Full Post]

Src family kinases promote silencing of ATR-Chk1 signaling in termination of DNA damage checkpoint.

905 | Jul 07 2018

Fukumoto Y, et al. suggested a model according to which Src family kinases send a termination signal between the completion of DNA repair and the initiation of checkpoint termination. [Read the Full Post]

Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells

853 | Jul 01 2018

Li H et al. indicated that the results from our study advance our understanding of host-ILTV interactions on a molecular level and provide experimental evidence that it is possible to control ILT via the manipulation of host-virus interactions. [Read the Full Post]

FcγRIIB mediates antigen-independent inhibition on human B lymphocytes through Btk and p38 MAPK

997 | Jun 29 2018

Tzeng SJ et al. found the importance of antigen-independent inhibition by FcγRIIB in the prevention from antibody-mediated autoimmune diseases and in the regulation of B cell homeostasis. [Read the Full Post]

Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo

1850 | Jun 18 2018

Karpel-Massler G et al. suggested that targeting deubiquitinases for glioma therapy is feasible and effective. [Read the Full Post]

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

2076 | Jun 18 2018

McGarry E et al. revealed a novel role for USP9X in the maintenance of genomic stability during DNA replication and provide potential mechanistic insights into its tumor suppressor role in certain malignancies. [Read the Full Post]

Impairment of hypoxia-induced HIF-1α signaling in keratinocytes and fibroblasts by sulfur mustard is counteracted by a selective PHD-2 inhibitor

3106 | Jun 10 2018

Deppe J, et al. described a pathomechanism by which SM negatively affects hypoxia-stimulated HIF-1α signaling in keratinocytes and fibroblasts and thus possibly contributes to delayed wound healing in SM-injured patients that could be treated with PHD-2 inhibitors. [Read the Full Post]

EGF-mediated EGFR/ERK signaling pathway promotes germinative cell proliferation in Echinococcus multilocularis that contributes to larval growth and development

1615 | Jun 08 2018

Cheng Z et al. demonstrated the contribution of EGF-mediated EGFR/ERK signaling to the regulation of germinative cells in E. multilocularis, and suggest the EGFR/ERK signaling as a potential therapeutic target for AE and perhaps other human cestodiasis. [Read the Full Post]

FcγRIIB-Independent Mechanisms Controlling Membrane Localization of the Inhibitory Phosphatase SHIP in Human B Cells

849 | Jun 02 2018

Pauls SD et al. indicated that FcγRIIB is not uniquely able to promote membrane recruitment of SHIP, but rather modulates its function via formation of distinct signaling complexes. [Read the Full Post]

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases

1611 | May 28 2018

Song X et al. provided insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Therapeutic implication of HER2 in advanced biliary tract cancer

1443 | May 10 2018

Nam AR et al. suggested that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. [Read the Full Post]

Identification of different ALK mutations in a pair of neuroblastoma cell lines established at diagnosis and relapse

1137 | May 02 2018

Chen L et al. showed that use both Sanger and targeted deep sequencing, this study describes the identification of distinct ALK mutations in these paired cell lines, including the rare R1275L mutation, which has not previously been reported in a neuroblastoma cell line. Analysis of the sensitivity of NBLW and NBLW-R cells to a panel of ALK inhibitors (TAE-684, Crizotinib, Alectinib and Lorlatinib) revealed differences between the paired cell lines, and overall NBLW-R cells with the F1174L mutation were more resistant to ALK inhibitor induced apoptosis compared with NBLW cells. This pair of cell lines represents a valuable pre-clinical model of clonal evolution of ALK mutations associated with neuroblastoma progression. [Read the Full Post]

Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2

1144 | May 01 2018

Gnani D et al. demonstrated that FAK depletion reduces HCC cell growth by affecting cancer-promoting genes including the pro-oncogene EZH2. Furthermore, we unveil a novel unprecedented FAK/EZH2 crosstalk in HCC cells, thus identifying a targetable network paving the way for new anticancer therapies. [Read the Full Post]

A Receptor Tyrosine Kinase Inhibitor, Dovitinib (TKI-258), Enhances BMP-2-Induced Osteoblast Differentiation In Vitro

2317 | Apr 29 2018

Lee Y et al. suggested that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders. [Read the Full Post]

Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells

1863 | Apr 29 2018

Chon HJ et al. provided new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway. [Read the Full Post]

Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects

1803 | Apr 24 2018

Carniti C et al. provided further evidence that JAK inhibition represents a new and potentially clinically relevant approach to GVHD prevention. [Read the Full Post]

Targeting synthetic lethality between the SRC kinase and the EPHB6 receptor may benefit cancer treatment

1087 | Apr 22 2018

Paul JM et al. indicated the observations are of potential practical importance, since TNBC is an aggressive heterogeneous malignancy with a very high rate of patient mortality due to the lack of targeted therapies, and our work indicates that FDA-approved SRC inhibitors may potentially be used in a personalized manner for treating patients with EPHB6-deficient TNBC. Our findings are also of a general interest, as EPHB6 is downregulated in multiple malignancies and our data serve as a proof of principle that EPHB6 deficiency may be targeted by small molecule inhibitors in the SL approach. [Read the Full Post]

Abl2 kinase phosphorylates Bi-organellar regulator MNRR1 in mitochondria, stimulating respiration

1323 | Apr 19 2018

Aras S et al. showed that binding of MNRR1 to COX is promoted by phosphorylation at tyrosine-99 and that this interaction stimulates respiration. We show that phosphorylation of MNRR1 takes place in mitochondria and is mediated by Abl2 kinase (ARG). A family with Charcot-Marie-Tooth disease type 1A with an exaggerated phenotype harbors a Q112H mutation in MNRR1, located in a domain that is necessary for transcriptional activation by MNRR1. Furthermore, the mutation causes the protein to function suboptimally in the mitochondria in response to cellular stress. The Q112H mutation hinders the ability of the protein to interact with Abl kinase, leading to defective tyrosine phosphorylation and a resultant defect in respiration. [Read the Full Post]

Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455

1300 | Apr 16 2018

Wu D et al. revealed that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly. [Read the Full Post]

The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis

2185 | Apr 11 2018

Shao X et al. indicated that our study is the first to evaluate the synergy of TAK165 and ATRA in AML cell differentiation and to assess new opportunities for the combination of TAK165 and ATRA as a promising approach for future differentiation therapy. [Read the Full Post]

Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area

1244 | Apr 10 2018

Dutton JW 3rd et al. supported the possibility that ALK might be a novel target of pharmacotherapy for reducing excessive alcohol consumption. [Read the Full Post]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

3306 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors

1160 | Apr 02 2018

Martinho O et al. proposed that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients. [Read the Full Post]

The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition

1275 | Mar 31 2018

Mologni L et al. supported the use of combination strategies with PIM and PI3K inhibitors as effective treatment for PCa cases. [Read the Full Post]

FYN promotes breast cancer progression through epithelial-mesenchymal transition

2112 | Mar 29 2018

Xie YG et al. found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. [Read the Full Post]

Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia

2087 | Mar 23 2018

Akahane K et al. supported selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL. [Read the Full Post]

Prolactin signaling through focal adhesion complexes is amplified by stiff extracellular matrices in breast cancer cells

1270 | Mar 18 2018

Barcus CE et al. suggested that PRL signaling to FAK and SFKs may be useful targets in clinical aggressive ERα+ breast carcinomas. [Read the Full Post]

METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion

0 | Mar 18 2018

Zhang Z et al. identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention. [Read the Full Post]

NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells

1747 | Mar 15 2018

Xu Z et al. indicated that overexpression of NF-YA contributes to tumor angiogenesis through EZH2-STAT3 signaling in human melanoma cells, highlighting NF-YA as a potential therapeutic target in human melanoma. [Read the Full Post]

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy

1601 | Mar 15 2018

Yun JH et al. suggested the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. [Read the Full Post]

E-cadherin expression is correlated with focal adhesion kinase inhibitor resistance in Merlin-negative malignant mesothelioma cells

1296 | Feb 19 2018

Kato T et al. suggested that E-cadherin serves as a predictive biomarker for molecular target therapy with FAK inhibitors for patients with mesothelioma and that its expression endows MM cells with resistance to FAK inhibitors. [Read the Full Post]

Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4

1505 | Feb 17 2018

Tian L et al. indicated Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer. [Read the Full Post]

Dihydroartemisin inhibits glioma invasiveness via a ROS to P53 to β-catenin signaling

4438 | Feb 16 2018

Que Z et al. indicated that DHA inhibited the migration and invasion of human glioma cells with different types of p53 via different pathways. [Read the Full Post]

Development of Novel Patient-Derived Preclinical Models from Malignant Effusions in Patients with Tyrosine Kinase Inhibitor-Resistant Clear Cell Renal Cell Carcinoma

1482 | Feb 02 2018

Jang J et al. suggested that the PDC-PDX preclinical model we developed using malignant effusions can be a useful preclinical model to interrogate sensitivity to targeted agents based on genomic alterations. [Read the Full Post]

3D microtumors in vitro supported by perfused vascular networks

1841 | Feb 02 2018

Sobrino A et al. indicated that tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. [Read the Full Post]

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

0 | Feb 01 2018

Kim HK et al. considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials. [Read the Full Post]

Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease

1695 | Jan 24 2018

Bukong TN et al. demonstrated a novel, functional, and multicellular role for SYK phosphorylation in modulating immune cell-driven liver inflammation, hepatocyte cell death, and steatosis at different stages of ALD. [Read the Full Post]

Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

1085 | Jan 21 2018

Zhang J et al. suggested that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. [Read the Full Post]

Arsenic trioxide and all-trans-retinoic acid selectively exert synergistic cytotoxicity against FLT3-ITD AML cells via co-inhibition of FLT3 signaling pathways

1548 | Jan 13 2018

Wang LN et al. provided experimental evidence that supports further exploration of ATO/ATRA in FLT3-ITD AML in vivo and warrants a clinical evaluation of regimens comprising an ATO/ATRA combination. [Read the Full Post]

Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification

2387 | Jan 11 2018

Pan B et al. provided new insights into histone acetylation mechanisms of EGCG treatment that may contribute to the prevention of CDD in ageing populations. [Read the Full Post]

Sunitinib Treatment Enhances Metastasis of Innately Drug-Resistant Breast Tumors

0 | Jan 02 2018

Wragg JW et al. unravel specific features of antiangiogenic resistance, with potential therapeutic implications. [Read the Full Post]

Adaptive and Acquired Resistance to EGFR Inhibitors Converge on the MAPK Pathway

1492 | Jan 01 2018

Ma P et al. demonstrated that adaptive and acquired resistance to EGFR inhibitors can converge on the same pathway and credential cotargeting EGFR and MAPK as a promising therapeutic approach in EGFR mutant tumors. [Read the Full Post]

Tyrosine receptor kinase B is a drug target in astrocytomas

3236 | Dec 31 2017

Ni J et al. proposed NTRK2 as a potential therapeutic target in the subset of astrocytoma patients defined by QKI-NTRK2 fusion. [Read the Full Post]

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non-Small Cell Lung Cancer

1988 | Dec 25 2017

Ikeda S et al. suggested that expression of PD-L1 protein is upregulated by the simultaneous amplification of the PD-L1 and JAK2 genes through JAK-STAT signaling in NCSLC. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

0 | Dec 24 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells

1921 | Dec 24 2017

Zhang Y et al. provided novel insights into the mechanism of ErbB2 inhibition by neratinib. [Read the Full Post]

Dasatinib inhibits actin fiber reorganization and promotes endothelial cell permeability through RhoA-ROCK pathway

2574 | Dec 21 2017

Dasgupta SK et al. suggested that ROCK inhibitors could serve as therapeutic modalities to ameliorate the dasatinib-induced pulmonary changes. [Read the Full Post]

Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258) and its Therapeutic Implications

2153 | Dec 16 2017

Yadav SS et al. observed that both androgen receptor (AR) positive and AR-negative PCa cells differentiate into a NE phenotype upon treatment with Dovitinib. [Read the Full Post]

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

1921 | Dec 15 2017

Hsieh MS et al. concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. [Read the Full Post]

Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells

4053 | Dec 10 2017

Abraham SA et al. found that LSCs can be eradicated. [Read the Full Post]

MET Copy Number Gain Is Associated with Gefitinib Resistance in Leptomeningeal Carcinomatosis of EGFR-mutant Lung Cancer

2127 | Dec 10 2017

Nanjo S et al. suggested that combination therapy with MET inhibitors may be promising for controlling leptomeningeal carcinomatosis that acquires resistance to EGFR-TKIs [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

0 | Dec 06 2017

Gower A et al. showed that EMT does not drive resistance to ALK inhibitors and HSP90 inhibition demonstrates more efficacy when further ALK inhibition may not. This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma

1776 | Dec 06 2017

Shimada Y et al. showed that rare oncogenic aberrations, such as the ALK fusion and RRAS mutation, may drive pancreatic carcinogenesis independent of the KRAS mutation. [Read the Full Post]

Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling

1146 | Dec 05 2017

Ji C et al. concluded that gremlin protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin could be further tested as a novel anti-UV skin protectant. [Read the Full Post]

Arsenite suppresses angiogenesis of vascular endothelial cells mediated by Platelet Derived Growth Factor Receptor-beta

1314 | Dec 03 2017

Wang X et al. concluded that arsenite suppressed the angiogenesis of the vascular endothelial cells, that this effect is mediated by PDGFR-beta, and postulate that it might contribute to the injuries of blood vessel in arsenism. [Read the Full Post]

Complex Roles of Annexin A2 in Host Blood-Brain Barrier Invasion by Cryptococcus neoformans

1276 | Nov 27 2017

Fang W et al. indicated that AnxA2 played complex roles in traversal of C. neoformans across host BMECs, which might be dependent on downstream cofilin to inhibit fungal adhesion but rely on its partner S100A10 to promote cryptococcal transcytosis. [Read the Full Post]

Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells

2011 | Nov 23 2017

Qiao L et al. confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

0 | Nov 21 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypic transition of corpus cavernosum smooth muscle in rats

1223 | Nov 09 2017

Yan JF et al. indicated that through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy. [Read the Full Post]

Spleen Tyrosine Kinase Mediates EGFR Signaling to Regulate Keratinocyte Terminal Differentiation

1472 | Nov 09 2017

Wu NL et al. unraveled the role of Syk in EGFR-mediated signaling and reveals regulatory roles of Syk in keratinocyte differentiation, suggesting the clinical potential of topical or systemic Syk inhibitors in the treatment of skin diseases with aberrant differentiation. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

0 | Nov 08 2017

Simioni C et al. indicated that co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Quantitative proteomics of breast tumors: Tissue quality assessment to clinical biomarkers

2019 | Nov 06 2017

Chen Y, et al. showed that combined with biomarkers for tissue quality and histological content are implemented in a three-tier multiplexed assay platform, which is translated from cell line models into frozen tumor tissues banked from breast cancer patients. [Read the Full Post]

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

2241 | Nov 05 2017

Nairismägi ML et al. showed that inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. [Read the Full Post]

Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis

1856 | Nov 05 2017

Li DQ et al. showed that PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology. [Read the Full Post]

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein

0 | Nov 01 2017

Wang Y et al. provided a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions. [Read the Full Post]

S100B impairs glycolysis via enhanced poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogenase in rodent muscle cells

1553 | Oct 30 2017

Hosokawa K et al. concluded that S100B as a humoral factor may impair glycolysis in muscle cells independent of insulin action, and the effect may be attributed to the inhibition of GAPDH activity from enhanced poly(ADP-ribosyl)ation of the enzyme. conclude that S100B as a humoral factor may impair glycolysis in muscle cells independent of insulin action, and the effect may be attributed to the inhibition of GAPDH activity from enhanced poly(ADP-ribosyl)ation of the enzyme. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

0 | Oct 25 2017

Gower A et al. showed that EMT does not drive resistance to ALK inhibitors and HSP90 inhibition demonstrates more efficacy when further ALK inhibition may not. This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Novel Mechanisms for the Antifibrotic Action of Nintedanib

1940 | Oct 22 2017

Rangarajan S et al. showed that Nintedanib down-regulated protein and mRNA expression of extracellular matrix (ECM) proteins, fibronectin, and collagen 1a1 while inhibiting transforming growth factor (TGF)-β1-induced myofibroblast differentiation. Nintedanib also induced beclin-1-dependent, ATG7-independent autophagy. Nintedanib's ECM-suppressive actions were not mediated by canonical autophagy. Nintedanib inhibited early events in TGF-β signaling, specifically tyrosine phosphorylation of the type II TGF-β receptor, activation of SMAD3, and p38 mitogen-activated protein kinase. Nintedanib down-regulates ECM production and induces noncanonical autophagy in IPF fibroblasts while inhibiting TGF-β signaling. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Oct 19 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Resistance Mechanism against Trastuzumab in HER2-Positive Cancer Cells and Its Negation by Src Inhibition

1571 | Oct 16 2017

Jin MH et al. suggested that Src inhibition may be an effective measure to overcome trastuzumab resistance in HER2-positive cancer. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

0 | Oct 12 2017

Saha SK et al. provided a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

4216 | Oct 09 2017

Grygielewicz P et al. provide experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies

1715 | Oct 08 2017

Shaver TM et al. identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. [Read the Full Post]

Cabozantinib is selectively cytotoxic in acute myeloid leukemia cells with FLT3-internal tandem duplication (FLT3-ITD)

1622 | Oct 03 2017

Lu JW et al. showed that Clinical trials evaluating the efficacy of cabozantinib in acute myeloid leukemia (AML) with FLT3-ITD are warranted. [Read the Full Post]

In Vivo Visualization and Characterization of Epithelial-Mesenchymal Transition in Breast Tumors

1384 | Oct 03 2017

Zhao Z et al. provided a novel opportunity for visualizing tumor EMT at the single-cell level and may help to reveal the intricacies underlying tumor dynamics and treatment responses. [Read the Full Post]

An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells

0 | Oct 02 2017

Zhang HR et al. indicated that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression. [Read the Full Post]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

0 | Sep 27 2017

Virakul S et al. found that multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis

0 | Sep 14 2017

Kobayashi K et al. suggested that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

3210 | Sep 01 2017

Simioni C et al. showed that dephosphorylation of pAkt and pS6 showed the cytotoxicity of these compounds. Either single or combined administration of drugs against the different targets displayed inhibition of cellular viability associated with a concentration-dependent induction of apoptosis, cell cycle arrest in G0/G1 phase and autophagy, having the combined treatments a significant synergistic cytotoxic effect. Co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells

1452 | Aug 31 2017

Kim HS et al. showed that GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs. [Read the Full Post]

Oncogene swap as a novel mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor in lung cancer

1923 | Aug 31 2017

Mizuuchi H et al. analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of an oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, an "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene. [Read the Full Post]

An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells

4071 | Aug 16 2017

Zhang HR et al. indicated that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression. [Read the Full Post]

Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398

1700 | Aug 15 2017

Datta J et al. suggested a role for Akt pathway in mediating acquired resistance to FGFR inhibition. [Read the Full Post]

Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma

1420 | Aug 13 2017

Hanes R et al. indicated that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2. [Read the Full Post]

ZFX Facilitates Cell Proliferation and Imatinib Resistance in Chronic Myeloid Leukemia Cells

1510 | Aug 10 2017

Jingjing Wu et al. suggested that ZFX is a novel oncogene promoting cell proliferation and inducing imatinib resistance via PI3K/Akt signaling pathway. ZFX may represent a potential therapeutic target in CML. [Read the Full Post]

Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant

0 | Aug 04 2017

Hamasy A et al. identified three potential ibrutinib resistance scenarios for cysteine 481 replacement. [Read the Full Post]

Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment

2917 | Aug 01 2017

Appelbe OK et al. suggest repurposing image-guided radiotherapy as a tool to guide cancer nanomedicine delivery, enhancing local control for primary tumors and metastatic disease while limiting systemic toxicity. [Read the Full Post]

Y-632 inhibits heat shock protein 90 (Hsp90) function by disrupting the interaction between Hsp90 and Hsp70/Hsp90 organizing protein, and exerts antitumor activity in vitro and in vivo

2805 | Aug 01 2017

Wang W et al. believe that Y-632, acting as a novel small-molecule inhibitor of the Hsp90-Hsp70/Hsp90 organizing protein complex, has great potential to be a promising Hsp90 inhibitor for cancer therapy, such as for imatinib-resistant leukemia. [Read the Full Post]

Sunitinib Treatment Enhances Metastasis of Innately Drug-Resistant Breast Tumors

2368 | Jul 31 2017

Wragg JW et al. unraveled specific features of antiangiogenic resistance, with potential therapeutic implications. [Read the Full Post]

Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model

2323 | Jul 28 2017

Omachi K et al. suggested that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

2380 | Jul 28 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients. [Read the Full Post]

PI3 Kinase Pathway and MET Inhibition is Efficacious in Malignant Pleural Mesothelioma

1799 | Jul 27 2017

Kanteti R et al. showed that a combination of crizotinib with BKM120 was highly synergetic in inhibiting MPM tumor growth. In conclusion our findings suggest that dual inhibition of PI3K and MET pathway is an effective strategy in treating MPM as compared to a single agent. [Read the Full Post]

Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1

1898 | Jul 27 2017

Zhu K et al. suggested that EGCG has an anticancer effect on OS cells, at least partially, through regulating miR-1/c-MET interaction. [Read the Full Post]

17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib

5687 | Jul 26 2017

Girgert R et al. showed that reduction of GPER expression is a promising therapeutic approach for TNBC. [Read the Full Post]

cMET inhibitor crizotinib impairs angiogenesis and reduces tumor burden in the C3(1)-Tag model of basal-like breast cancer

1915 | Jul 26 2017

Cozzo AJ et al. showed cMET inhibition by crizotinib limited tumor development and microvascular density in basal-like tumor-bearing mice but did not appear to be an effective preventive agent for BBC. [Read the Full Post]

Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

2577 | Jul 17 2017

Liu R et al. conclude that the endogenous EPO/EPOR signaling pathway may contribute to the protective effects of ALA in the retina after ONC injury. [Read the Full Post]

Metalloproteinase-9 contributes to endothelial dysfunction in atherosclerosis via protease activated receptor-1

1282 | Jul 13 2017

Florence JM et al. demonstrated that metalloproteinase-9 could activate endothelial cells and induce their apoptosis via cleavage of protease activated receptor-1. In summary, better understanding of metalloproteinase-9's pathogenic capabilities as well as novel signaling pathways involved may lead to development of treatments which may provide additional benefits to atherosclerosis patients with a history of second hand smoke exposure. [Read the Full Post]

MET Inhibition in Clear Cell Renal Cell Carcinoma

0 | Jul 01 2017

Xie Z et al. provided further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

2745 | Jun 29 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

3650 | Jun 27 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

A PGC1α-mediated transcriptional axis suppresses melanoma metastasis

2959 | Jun 23 2017

Luo C et al. revealed that PGC1α maintains mitochondrial energetic metabolism and suppresses metastasis through direct regulation of parallel acting transcriptional programs. [Read the Full Post]

Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution.

1645 | Jun 17 2017

Zhao B, et al. identified new strategies to treat dynamic tumor vulnerabilities. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

2850 | Jun 16 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Functionalized gold nanoparticles improve afatinib delivery into cancer cells

2700 | Jun 16 2017

Coelho SC et al. found that PEGAuNPs with afatinib is a promising antitumor delivery system for cancer therapy as it improves drug efficacy, allowing a reduction in drug dose used and minimizing possible toxicity-related side effects. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

5877 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk

2098 | Jun 11 2017

Peng M, et al. found these two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

3588 | Jun 11 2017

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

The new and recurrent FLT3 juxtamembrane deletion mutation shows a dominant negative effect on the wild-type FLT3 receptor

1742 | May 31 2017

Sandhöfer N et al. that FLT3 p.Q569Vfs*2 is the first FLT3 mutation with a dominant negative effect on the WT receptor. [Read the Full Post]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

0 | May 28 2017

Ochi N et al. found that pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. [Read the Full Post]

Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors

1863 | May 28 2017

Yadav M et al. found that HRs play critical roles in anti-cancer effects of gefitinib in both EGFR-deficient and EGFR-rich environments. [Read the Full Post]

The Promoting Effect of Radiation on Glucose Metabolism in Breast Cancer Cells under the Treatment of Cobalt Chloride

2061 | May 27 2017

Zhao CB et al. found that the combination of radiation and hypoxia could promote the glucose metabolism. [Read the Full Post]

The Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway

2927 | May 26 2017

Du HY et al. found that IL-33 plays an important role in the pathogenesis of immune inflammatory responses in AD, which might be a possible therapeutic target in the treatment of AD. [Read the Full Post]

Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3

0 | May 24 2017

Heiss EH et al. demonstrated that increased aerobic glycolysis is an important factor for the motility of activated VSMC and that the anti-migratory property of I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 signaling axis. [Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

2393 | May 22 2017

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters [Read the Full Post]

FGFR3-TACC3 fusion proteins act as naturally occurring drivers of tumor resistance by functionally substituting for EGFR/ERK signaling

1792 | May 21 2017

Daly C, et al. found that FGFR3-TACC3 fusion proteins may represent a novel mechanism of acquired resistance in EGFR-dependent cancers of multiple cell lineages. [Read the Full Post]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells.

0 | May 18 2017

Khan IA et al. have identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. [Read the Full Post]

Identification of Novel Inhibitors of the Type I Interferon Induction Pathway Using Cell-Based High-Throughput Screening

2766 | May 17 2017

Gage ZO et al. demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. [Read the Full Post]

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

3720 | May 17 2017

Miller RE et al. suggested that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. [Read the Full Post]

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery

0 | May 16 2017

Sun H et al. showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

3381 | May 15 2017

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line

0 | May 14 2017

Treda C et al. showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. [Read the Full Post]

A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo

2382 | May 12 2017

Dey J et al. found a platform for rapid, quantitative assessment of multiple drug combinations simultaneously in solid tumors In vivo. [Read the Full Post]

Src as a Therapeutic Target in Biliary Tract Cancer.

0 | May 11 2017

Nam AR et al. suggested that Src might be a potential therapeutic target in BTC. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

0 | May 09 2017

Saafan H et al.found that knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

0 | May 08 2017

Saafan H et al. found that knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling.

4208 | May 07 2017

Shimada T et al suggested that neuritin and FGF cooperate in inducing mossy fiber sprouting through FGF signaling. Together, these results suggest that FGF and neuritin-mediated axonal branch induction are involved in the aggravation of epilepsy. [Read the Full Post]

EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen

0 | May 07 2017

Scheipl S et al provided evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. [Read the Full Post]

The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling

0 | May 06 2017

Song S et al. identified a novel mechanism to reveal the formation of EndoMT in PAH, and implied that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease. [Read the Full Post]

The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling

1661 | Apr 29 2017

Song S et al. identified a novel mechanism to reveal the formation of EndoMT in PAH, and imply that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease. [Read the Full Post]

MAP3K19-Is-a-Novel-Regulator-of-TGF-B-Signaling-That-Impacts-Bleomycin-Induced-Lung-Injury-and-Pulmonary-Fibrosis

8749 | Apr 23 2017

Boehme SA et al suggested that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease. [Read the Full Post]

BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

0 | Apr 20 2017

Habata S et al. suggested that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers. [Read the Full Post]

Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1

2785 | Apr 19 2017

Baris S et al. found thatJAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation. [Read the Full Post]

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma

1776 | Apr 15 2017

Cidre-Aranaz F et al. suggested that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

7246 | Apr 09 2017

Collectively, Wu C et al revealed, for the first time, a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells

1593 | Apr 07 2017

Abe M et al. found that FLT3-ITD is capable of inhibiting FLT3-ITD+ cell proliferation through the p21/Pbx1 axis and that treatments that antagonize FLT3-ITD contribute to the subsequent development of cells that are refractory to a FLT3-ITD inhibitor by disrupting p21 expression. [Read the Full Post]

Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models

1878 | Apr 05 2017

Tsimafeyeu I et al showed that alofanib is a potent FGFR2 inhibitor and provide strong rationale for its evaluation in patients with FGFR2-driven cancers. [Read the Full Post]

Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation

2937 | Apr 03 2017

Huang A et al revealed a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. [Read the Full Post]

iRGD-Decorated Polymeric Nanoparticles for the Efficient Delivery of Vandetanib to Hepatocellular Carcinoma: Preparation and in Vitro and in Vivo Evaluation

1586 | Apr 01 2017

Wang J et al. demonstrated that reformulating targeted therapeutic agents in NPs permits their systemic administration and thus significantly improves the potency of currently available, orally delivered agents. [Read the Full Post]

Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK–Positive Anaplastic Large Cell Lymphoma

0 | Mar 15 2017

Ceccon M et al. found the knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI-resistant cases. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Mar 13 2017

Sampson VB et al suggested that potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization

0 | Mar 12 2017

Lin YC et al found that the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3-related immune diseases. [Read the Full Post]

Malassezia yeasts activate the NLRP3 inflammasome in antigen-presenting cells via Syk-kinase signalling

0 | Mar 12 2017

Kistowska M et al identified Malassezia spp. as potential strong inducers of pro-inflammatory responses when taken up by antigen-presenting cells and identify C-type lectin receptors and the NLRP3 inflammasome as crucial actors in this process. [Read the Full Post]

GRP78 confers the resistance to 5-FU by activating the c-Src/LSF/TS Axis in hepatocellular carcinoma

1864 | Mar 11 2017

Gu YJ, et al. further identified that GRP78 interacts physically with c-Src through its ATPase domain and promotes the phosphorylation of c-Src, which in turn increases the expression of LSF in the nucleus. Together, GRP78 confers the resistance to 5-FU by up-regulating the c-Src/LSF/TS axis via its ATPase domain. [Read the Full Post]

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

0 | Mar 11 2017

Chihara K et al. suggested that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. [Read the Full Post]

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

0 | Mar 11 2017

Angata T et al found that Siglec-14 and its downstream signaling pathway facilitate the "infection-inflammation-exacerbation" axis of COPD disease progression, and may represent promising targets for therapeutic intervention. [Read the Full Post]

Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway

0 | Mar 08 2017

Ying R et al. revealed that H2S could protect against ER stress-induced EndMT through Src pathway, which may be a novel role for the cardioprotection of H2S. [Read the Full Post]

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer

0 | Feb 17 2017

Manteghi S et al. establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

2108 | Feb 08 2017

This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

2995 | Feb 06 2017

Kim TM, et al.'s result shows that Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation. [Read the Full Post]

EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs

2646 | Feb 05 2017

Kobayashi Y, et al.’‘s result shows that’Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells.

0 | Feb 05 2017

Ishibashi T, et al.'s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/ Mammalian Target of Rapamycin (mTOR) Axis is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

1931 | Feb 04 2017

Makinoshima H, et al.‘s results suggest that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells. [Read the Full Post]

Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice

3320 | Jan 28 2017

The activation of STAT3 pathway might play an important part in the pathogenesis of radiation-induced lung injury. The protective effects of delayed treatment of WP1066 suggested STAT3 signaling could be a therapeutic target for radiation pneumonitis. [Read the Full Post]

Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK–Positive Anaplastic Large Cell Lymphoma

3820 | Jan 23 2017

Ceccon M, et al.'s knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI-resistant cases. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Jan 21 2017

In Sampson VB, et al.'s summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Malassezia yeasts activate the NLRP3 inflammasome in antigen-presenting cells via Syk-kinase signalling

1477 | Jan 20 2017

Kistowska M, et al.'s results identify Malassezia spp. as potential strong inducers of pro-inflammatory responses when taken up by antigen-presenting cells and identify C-type lectin receptors and the NLRP3 inflammasome as crucial actors in this process. [Read the Full Post]

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

1599 | Jan 19 2017

Angata T, et al. found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the "infection-inflammation-exacerbation" axis of COPD disease progression, and may represent promising targets for therapeutic intervention. [Read the Full Post]

Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization

1431 | Jan 19 2017

Lin YC, et al.'s results reveal a new molecular pathway through which Syk promotes NLRP3 inflammasome formation, resulting from the phosphorylation of ASC. Thus, the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3-related immune diseases. [Read the Full Post]

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

1428 | Jan 18 2017

Chihara K, et al.'s data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

1830 | Jan 03 2017

The study of Mol Oncol's warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

2037 | Jan 02 2017

Makinoshima H et al. suggested that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells. [Read the Full Post]

EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs

2480 | Jan 02 2017

Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations. [Read the Full Post]

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

3235 | Dec 30 2016

Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation. [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells

2821 | Dec 29 2016

Ishibashi T, et al.‘’s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

MET Inhibition in Clear Cell Renal Cell Carcinoma

2453 | Dec 23 2016

Xie Z et al. provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. [Read the Full Post]

Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease

2130 | Dec 17 2016

Bukong TN et al. demonstrated a novel, functional, and multicellular role for SYK phosphorylation in modulating immune cell-driven liver inflammation, hepatocyte cell death, and steatosis at different stages of ALD. [Read the Full Post]

Reconstructing the temporal progression of HIV-1 immune response pathways

2823 | Dec 13 2016

Jain S et al. experimentally validated several of TimePaths' predictions highlighting the usefulness of temporal models. [Read the Full Post]

Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant

1646 | Dec 11 2016

Hamasy A et al. identified three potential ibrutinib resistance scenarios for cysteine 481 replacement: (1) Serine, being catalytically active and therefore predominating among patients. (2) Threonine, also being catalytically active, but predicted to be scarce, because two nucleotide changes are needed. (3) As BTK variants replaced with other residues are catalytically inactive, they presumably need compensatory mutations, therefore being very scarce. [Read the Full Post]

Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis

3052 | Dec 02 2016

Kobayashi K et al. suggested that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis. [Read the Full Post]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

5625 | Nov 26 2016

Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies

2696 | Nov 21 2016

Shaver TM et al. identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

4493 | Nov 16 2016

Saha SK et al. showed that IDHm ICC cells have a unique dependency on SRC and suggested that dasatinib may have therapeutic benefit against IDHm ICC. [Read the Full Post]

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein

2244 | Nov 09 2016

Wang Y et al. provides a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions. [Read the Full Post]

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer.

3133 | Nov 08 2016

Manteghi S, et al.found that we establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

2759 | Oct 25 2016

Ochi N et al. found that pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. [Read the Full Post]

Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors

1979 | Oct 25 2016

Yadav M et al. found that HRs play critical roles in anti-cancer effects of gefitinib in both EGFR-deficient and EGFR-rich environments. [Read the Full Post]

Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3'-monoxime

2479 | Oct 21 2016

Heiss EH et al. demonstrated that increased aerobic glycolysis is an important factor for the motility of activated VSMC and that the anti-migratory property of I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 signaling axis. [Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

3133 | Oct 19 2016

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters. [Read the Full Post]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells

3302 | Oct 14 2016

Khan IA et al. identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. [Read the Full Post]

EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line

3357 | Oct 14 2016

Treda C et al. showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

4269 | Oct 13 2016

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

2239 | Oct 11 2016

Habata S et al. suggested that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers. [Read the Full Post]

Src as a Therapeutic Target in Biliary Tract Cancer

2166 | Oct 10 2016

Nam AR et al. suggested that Src might be a potential therapeutic target in BTC. [Read the Full Post]

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery

2726 | Oct 10 2016

Sun H et al. showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds and performed much better than Autodock, suggesting that the proposed strategy is a powerful tool in structure-based virtual screening. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach

2839 | Oct 08 2016

Saafan H et al. identified that differential proteins in the EGFR interactome of HCC4006rERLO0.5 cells could be related to multiple resistance mechanisms including alterations in growth factor receptor expression, cellular remodelling processes suggesting epithelial-to-mesenchymal transition as well as alterations in downstream signalling. [Read the Full Post]

EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen

3150 | Sep 30 2016

Scheipl S et al. provided evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling

2588 | Sep 29 2016

Shimada T, et al. revealed the molecular mechanism underlying mossy fiber sprouting. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

3414 | Sep 12 2016

Wu C et al. revealed that a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation

0 | Sep 08 2016

Huang A, et al. revealed a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. [Read the Full Post]

Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models

2097 | Sep 08 2016

Tsimafeyeu I, et al. found that alofanib is a potent FGFR2 inhibitor and provide strong rationale for its evaluation in patients with FGFR2-driven cancers. [Read the Full Post]

Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway

2014 | Sep 02 2016

Ying R, et al. revealed that H2S could protect against ER stress-induced EndMT through Src pathway, which may be a novel role for the cardioprotection of H2S. [Read the Full Post]

Tcfap2c acts as a key factor in mammary tumorigenesis

4987 | Mar 27 2015

Park et al. conducted a serious experiments to gain greater insight into functions of TFAP2C on mammary tumorigeneisis in MMTV-Neu transgenic female mice. [Read the Full Post]

GPRC5A directly inhibits EGFR signaling to suppress lung tumorigenesis

6248 | Mar 20 2015

Zhong et al. revealed that GPRC5A negatively regulates EGFR signaling and its downstream signaling STAT3. [Read the Full Post]

Molecular changes of the transformation of NSCLC to SCLC TKI-resistant EGFR mutant cancers

4863 | Mar 16 2015

Niederst et al. demonstrated the molecular changes occur in NSCLC to small-cell lung cancer (SCLC) transformed TKI-resistant EGFR mutant cancers. [Read the Full Post]

AXL regulates cetuximab resistance in HNSCC and NSCLC

6497 | Mar 13 2015

Brand et al. demonstrated that AXL-EGFR signaling positive feedback loop is one of the mechanism of developing cetuximab resistance. [Read the Full Post]

αB-crystallin induces by matrix detachment via ERK is critical in inhibition of anoikis

7887 | Mar 05 2015

Malin et al. identified an matrix detachment-induced antiapoptotic molecular chaperone, αB-crystallin, confers anoikis resistance. [Read the Full Post]

Inactivating mutations of SMARCE1 promotes EGFR expression and suppress the responses to MET and ALK inhibitors in lung cancer

6652 | Feb 26 2015

The study conducted by Papadakis et al. showed inactivating mutations in SMARCE1 gene, which encodes SWI/SNF subunit, upregulate EGFR expression and induce resistance to MET and ALK inhibitors in non-small cell lung cancers (NSCLCs). [Read the Full Post]

A novel role of Semaphorin3A on the increase of vascular permeability

6198 | Jan 28 2015

Hou et al. identified Semaphorin3A (Sema3A) as a critical factor mediates vascular permeability and contributes to ischemic brain damage. [Read the Full Post]

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

15352 | Jan 23 2015

Dubrovsky et al. developed an antibody, ESKM, which is therapeutically effective on acute and chronic leukemias in murine models. [Read the Full Post]

The new finding of PI3K signaling regulation provides a novel therapeutic strategy for luminal breast cancer

8456 | Jan 15 2015

Costa et al. found the high efficiency of p110α inhibition by BYL719 is attenuated due to p110β accumulation. [Read the Full Post]

Tofacitinib promotes myeloid-derived suppressor cells expansion and reduces disease severity of arthritis SKG mice

6945 | Jan 14 2015

Nishimura et al. revealed that tofacitinib has effect on promoting MDSCs expansion and ameliorating arthritis in SKG mice. [Read the Full Post]

An unusual mechanism of ERBB4 in regulating tumor related gene expression

9639 | Jan 06 2015

Haskins et al. found ERBB4 activated the transcriptional coactivator YAP by binding to its ligand neuregulin 1 (NRG1), to regulate gene expression of cancer cells. [Read the Full Post]

Two states of BRAFV600 mutant melanoma that related to MAPK inhibition resistance

7230 | Dec 31 2014

Konieczkowski et al. revealed the mechanism of MAPK inhibition on BRAFV600 mutant melanomas. [Read the Full Post]

ABL1, a new target of oxidative stress related rental cancer

5531 | Dec 19 2014

Sourbier et al. used hereditary kidney cancers as a model to investigate mechanism-based therapeutic interventions by metabolic adaptations. They found the activation of ABL1, an proto-oncogene, is critical in tumors that relate to glycolysis and oxidative stress. [Read the Full Post]

The inhibition of JAK signaling promotes the conversion from white to brown adipocytes

8551 | Dec 17 2014

By using a screening platform of small molecules identification, Moisan et al. found two inhibitors of JAK signaling were able to convert white adipocytes to brown adipocytes. [Read the Full Post]

VEFG/SphK pathway plays an important role in Niemann-Pick type C disease

4381 | Dec 03 2014

Lee et al. identified the defective of sphingosine kinase (SphK) and vascular endothelial growth factor (VEGF) activities are main signaling that promotes sphingosine storage. [Read the Full Post]

KIAA1199 provides a connection between oncogenic signaling of NF-κB and EGFR

6437 | Dec 01 2014

Shostak et al. showed the connection between the two oncogenic cascades by identifying a key factor, KIAA1199, that associated with human papillomavirus (HPV) infection. [Read the Full Post]

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

11351 | Nov 24 2014

Dechow et al. determined GP130/JAK/STAT3 signaling pathway is sufficient to induce MM generation in mice retroviral murine BM transduction-transplantation model. [Read the Full Post]

The mechanism of drug resistance in BRAF (V600E) mutant melanoma

9724 | Nov 19 2014

Sun et al. demonstrated the resistance of BRAF (V600E) is reversible and adaptive. The process involves several transduction factors, such as EGFR, PDGFRB, TGF-β, and SOX10. [Read the Full Post]

Combination of PI3K/mTOR and EGFR inhibitors suppresses KRAS-mutant colorectal cancer

7152 | Nov 14 2014

Belmont et al. demonstrated combination of PI3K/mTOR and EGFR inhibitors may become a novel therapy in patients with KRAS-mutant CRC. [Read the Full Post]

Interactions between Slit-Robo and JAK-STAT signaling in regulation of stem cell-niche adhesion

8890 | Nov 10 2014

Rachel R. Stine et al. found Slit-Robo and JAK-STAT signaling pathways play key roles in stem cells competition within their niches. [Read the Full Post]

FGF21 is not required for CR-mediated IGF-1 reduction or cell proliferation inhibition

8158 | Nov 06 2014

Thompson et al. found that, in response to moderate CR, phosphorylated STAT5 may act as a key molecule, and FGF21 was not required for the down-regulation of IGF-1 expression level or cell proliferation rates. [Read the Full Post]

Targeting ALK and ERK5 is a new strategy for neuroblastoma treatment

4611 | Nov 04 2014

Umapathy et al. found kinase ERK5 regulates Anaplastic lymphoma kinase (ALK) induced MYCN transcription and proliferation of neuroblastoma. The results indicates that combination therapy of inhibiting ALK and ERK5 may be a novel strategy for ALK-positive neuroblastoma patients. [Read the Full Post]

JAK2 and MPL are two main regulators of TPO-induced megakaryopoiesis

7314 | Nov 03 2014

Megakaryopoiesis is regulated by TPO, which activates multiple signaling molecules. Besancenot et al. demonstrated that the protein levels of JAK2 and MPL determine TPO-induced megakaryopoiesis. [Read the Full Post]

Endocrine therapy has become the most important systemic treatment

4782 | Mar 10 2014

Imatinib is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM, respectively. [Read the Full Post]

Afatinib is a drug approved in much of the world

4527 | Mar 07 2014

BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. [Read the Full Post]

Linifanib is a structurally novel potent inhibitor of RTK

3612 | Mar 03 2014

Linifanib shows inhibitory to Kit, PDGFRβ and Flt4 with IC50 of 14 nM, 66 nM and 190 nM in kinases assay. [Read the Full Post]

E7080 is a multi kinase inhibitor that is being investigated for the treatment of various

3923 | Feb 27 2014

E7080 (Lenvatinib) is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β. Phase 3. [Read the Full Post]

BGJ398 is a potent and selective FGFR inhibitor for FGFR

4097 | Feb 21 2014

BGJ398 also prevents VEGFR2 with low potency. [Read the Full Post]

Linifanib is a structurally novel potent inhibitor of receptor tyrosine kinases

3606 | Feb 20 2014

Linifanib shows inhibitory to Kit, PDGFRβ and Flt4 with IC50 of 14 nM, 66 nM and 190 nM in kinases assay. [Read the Full Post]

Dovitinib is currently under clinical investigation for hepatocellular carcinoma

4022 | Feb 19 2014

Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 of 25 nM. [Read the Full Post]

Cediranib is currently in double blind studies for the treatment

3871 | Feb 18 2014

Cediranib (AZD2171) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM [Read the Full Post]

XL184 is a small molecule inhibitor of the tyrosine kinases

3565 | Feb 14 2014

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM [Read the Full Post]

Cediranib is a potent inhibitor of vascular endothelial growth factor

3949 | Feb 10 2014

Cediranib suppresses PDGF-AA with IC50 of 0.04 μM in MG63 cell lines. [Read the Full Post]

Bosutinib is a tyrosine kinase inhibitor undergoing research

4274 | Feb 10 2014

Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM, respectively. [Read the Full Post]

Dasatinib is being evaluated for use in numerous other cancers

3946 | Feb 08 2014

Dasatinib is more effective than imatinib in inhibiting the proliferation of Ba/F3 cells expressing wild-type Bcr-Abl and Bcr-Abl mutants. [Read the Full Post]

We describe the mechanism of action of WP1130

0 | Feb 08 2014

WP1130 is a selective deubiquitinase inhibitor. [Read the Full Post]

E7080 is a multi kinase inhibitor that is being investigated

3091 | Jan 24 2014

E7080, as a potent inhibitor of in vitro angiogenesis, shows a significantly inhibitory effect on VEGF/KDR and SCF/Kit signaling. [Read the Full Post]

We describe the mechanism of action of WP1130

5200 | Jan 22 2014

WP1130 (Degrasyn) is a selective deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and also suppresses Bcr/Abl, also a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT). [Read the Full Post]

XL184 is currently undergoing clinical trials for the treatment of prostate

3136 | Jan 21 2014

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. [Read the Full Post]

PCI 32765 is an anticancer drug targeting B cell malignancies

3914 | Jan 20 2014

PCI-32765 shows the potent and irreversible inhibitory effect and selectivity for Btk enzymatic activity. [Read the Full Post]

WP1066 is a cell permeable AG 490 tyrphostin analog

6523 | Jan 15 2014

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. [Read the Full Post]

Bafetinib is a dual Bcr Abl and Lyn kinase inhibitor

4005 | Jan 15 2014

Bafetinib (INNO-406) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM/19 nM, does not inhibit the phosphorylation of the T315I mutant and is less potent to PDGFR and c-Kit. Phase 2. [Read the Full Post]

AZD0530 is a dual specific inhibitor of Src and Abl

3898 | Jan 13 2014

Saracatinib also potently inhibits other Src tyrosine kinase family members including c-Yes, Fyn, Lyn, Blk, Fgr, and Lck with IC50 from 4-10 nM. [Read the Full Post]

Bafetinib is a second generation tyrosine kinase inhibitor

3858 | Jan 06 2014

Bafetinib blocks WT Bcr-Abl autophosphorylation and its downstream kinase activity with IC50 of 11 nM and 22 nM in K562 and 293T cells [Read the Full Post]

Dasatinib is a rescription medicine used to treat adults

3494 | Dec 25 2013

Dasatinib is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of ＜1 nM, 0.8 nM and 79 nM, respectively. [Read the Full Post]

Neratinib is a highly selective HER2 and EGFR inhibitor

3426 | Dec 25 2013

Neratinib weakly inhibits tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, being 14- and 24-fold less active compared with HER2. [Read the Full Post]

Dasatinib is a cancer drug produced by Bristol Myers Squibb

3889 | Dec 23 2013

Dasatinib is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of ＜1 nM, 0.8 nM and 79 nM, respectively. [Read the Full Post]

AZD0530 is a dually active inhibitor of c Src and Bcr ABL

3345 | Dec 18 2013

Saracatinib (AZD0530) is a potent Src inhibitor with IC50 of 2.7 nM, and potent to c-Yes, Fyn, Lyn, Blk, Fgr and Lck; less active for Abl and EGFR (L858R and L861Q). [Read the Full Post]

Tandutinib is a small molecule inhibitor of the type

3811 | Dec 09 2013

Tandutinib has little activity against EGFR, FGFR, KDR, InsR, Src, Abl, PKC, PKA and MAPKs. [Read the Full Post]

BGB324 is a novel oral highly selective small molecule inhibitor

3533 | Dec 05 2013

R428 blocks the catalytic and procancerous activities of Axl. R428 inhibits Axl with low nanomolar activity and blocks Axl-dependent events [Read the Full Post]

Gefitinib is used to treat non small cell lung cancer in people

4485 | Dec 04 2013

Gefitinib (ZD-1839) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. [Read the Full Post]

Dovitinib is a small molecule multitargeted receptor tyrosine kinase inhibitor

4140 | Nov 27 2013

Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 of 25 nM. [Read the Full Post]

Cediranib is a potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases

2739 | Nov 25 2013

Cediranib inhibits VEGF-stimulated proliferation with IC50 of 0.4 nM. Cediranib suppresses PDGF-AA with IC50 of 0.04 μM in MG63 cell lines. [Read the Full Post]

NVP BHG712 is a specific EphB4 inhibitor with ED50 of 25 nM

2987 | Nov 18 2013

NVP-BHG712 is a specific EphB4 inhibitor with ED50 of 25 nM that discriminates between VEGFR and EphB4 inhibition . [Read the Full Post]

R428 inhibits angiogenesis in corneal micropocket and tumor models

4594 | Nov 13 2013

R428 is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 and InsR, EGFR, HER2, and PDGFRβ. [Read the Full Post]

Dasatinib is a novel potent and multi targeted inhibitor

2961 | Nov 11 2013

Dasatinib is more effective than imatinib in inhibiting the proliferation of Ba/F3 cells expressing wild-type Bcr-Abl and Bcr-Abl mutants, with the exception of T315I. [Read the Full Post]

Nilotinib is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia

2687 | Nov 07 2013

Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. [Read the Full Post]

WP1130 is a novel selective small molecular deubiquitinase

2778 | Nov 06 2013

Administration of WP1130 inhibits the growth of K562 tumors as well as both wildtype Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. [Read the Full Post]

XL184 is a small molecule inhibitor of the tyrosine kinases c Met

2796 | Nov 01 2013

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. [Read the Full Post]

Nilotinib is indicated for the treatment of adult patients

2690 | Oct 31 2013

Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induces apoptosis of HSCs, which is correlated with reduced bcl-2 expression. [Read the Full Post]

This study is designed to evaluate the efficacy and safety of tofacitinib

7127 | Oct 30 2013

Tofacitinib citrate inhibits IL-2-mediated human T cell blast proliferation and IL-15-induced CD69 expression with IC50 of 11 nM and 48 nM, respectively. [Read the Full Post]

IOX2 is a potent inhibitor of HIF 1 prolyl hydroxylase 2 with IC50

4737 | Oct 29 2013

IOX2 potently inhibits PHD2 (IC50 of 21 nM) with over 100-fold selectivity compared to inhibition of JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH (IC50s <100 μM). IOX2 is active in cells, inhibiting HIF-1α hydroxylation in RCC4 cells at 50 μM. [Read the Full Post]

Neratinib is a tyrosine kinase inhibitor under investigation

3044 | Oct 21 2013

Neratinib weakly inhibits tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, being 14- and 24-fold less active compared with HER2. [Read the Full Post]

Sunitinib was the first cancer drug simultaneously

3145 | Aug 06 2013

Sunitinib inhibits VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation with IC50 of 10 nM and 10 nM, respectively. [Read the Full Post]

XL-184 is a new chemical entity that inhibits VEGFR2

2940 | Jun 26 2013

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. [Read the Full Post]

Motesanib is an experimental drug candidate

3136 | May 16 2013

Motesanib Diphosphate has broad activity against the human VEGFR family, and displays >1000 selectivity against EGFR, Src, and p38 kinase. [Read the Full Post]

Nilotinib was approved as Tasigna in the America

3239 | Apr 24 2013

Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induces apoptosis of HSCs, which is correlated with reduced bcl-2 expression, increases p53 expression, cleavage of PARP, as well as increases expression of PPARγ and TRAIL-R. Nilotinib also induces cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1. [Read the Full Post]

IOX2 is a potent inhibitor of HIF1with IC50 of 21 nM

4600 | Apr 16 2013

IOX2 potently inhibits PHD2 (IC50 of 21 nM) with over 100-fold selectivity compared to inhibition of JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH (IC50s <100 μM). IOX2 is active in cells, inhibiting HIF-1α hydroxylation in RCC4 cells at 50 μM. [Read the Full Post]

Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases

3100 | Apr 08 2013

These include all receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), which play a role in both tumor angiogenesis and tumor cell proliferation. [Read the Full Post]

Quizartinib is currently under development for the treatment of acute myeloid leukaemia

4285 | Apr 03 2013

Quizartinib (AC220) is a small molecule receptor tyrosine kinase inhibitor that is currently under development for the treatment of acute myeloid leukaemia. Its molecular target is FLT3, also known as CD135 which is a proto-oncogene. [Read the Full Post]

Sunitinib was the first cancer drug simultaneously approved for two different indications

2939 | Apr 01 2013

Sunitinib Malate (Sutent, SU11248) is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit. [Read the Full Post]

Src inhibitors are promising therapy molecules for human cervical carcinomas

3078 | Jan 22 2013

Candida albicans is responsible for approximately 50% of all human life-threatening nosocomial fungal infections . Completion of its diploid genome sequence now provides a foundation for studies on C. albicans biology and SRC Inhibitors pathogenesis, and offers new opportunities for therapeutic intervention. [Read the Full Post]

Activation of the HIF pathway in cancer

4652 | Dec 20 2012

nhibiting c-MET (mesenchymal_epithelial transition factor) signaling is emerging as a promising strategy for a new class of targeted cancer therapies. Several c-MET inhibitors are in various stages of clinical development and have demonstrated activity in different tumor HIF pathway types. [Read the Full Post]

ALK inhibitors are potential anti cancer drugs that act on tumours with variations

2992 | Dec 19 2012

The ALK (anaplastic lymphoma kinase) gene encodes a tyrosine kinase belonging to the insulin receptor superfamily. ALK is abundantly expressed in neural tissue during embryogenesis, but levels fall during early development, so that in adults it is expressed only in rare scattered neural cells (Iwahara et al., 1997; Morris et al., 1997; Webb et al., 2009; Ardini et al., 2010). [Read the Full Post]

ALK Inhibitors has been recognized leading to the reorganization

4362 | Dec 05 2012

The significance of transition from preclinical to clinical studies has been recognized leading to the re-organization of research units into ALK Inhibitors translational groups bringing involved disciplines closer together. The intent is to leverage basic science to better support the translation of in vitro and in vivo preclinical data into clinical decisions [Read the Full Post]

Gefitinib were not considered clinically relevant

5270 | Nov 15 2012

There were no statistically significant differences in the mean percent baseline slopes over the 6 h of testing, and any Gefitinib differences were not considered clinically relevant [Read the Full Post]

Inhibition of KSP affects the formation of the bipolar spindle

4693 | Oct 30 2012

Inhibition of KSP affects the formation of the bipolar spindle for the separation and purification of chromosomes w During mitosis. This chromosome abnormality leads to programmed cell death in mitotic cells. Here we have shown that SB715992 cell death induced apoptosis significantly PC 3 prostate cancer cells [Read the Full Post]

EGFR INHIBITORS AGAINST THE CANCERS

4820 | Sep 12 2012

INHIBITION OF EGFR: Among those few cascades which play an important role in the functioning of cells, epidermal growth factor receptor or EGFR pathway is one that has a vital role in growth, survival and proliferation of cells. The importance of this cascade can only be observed and understood in case of development of tumors and fatal diseases related to the uncontrolled cell growth caused by the improper regulation of EGFR signaling pathway. Over or mutated expression of the EGFR is associated with different types of cancers like colon, lung and breast cancers and with multiform glioblastoma, anal and epithelial cancers. Therefore the treatment of these cancers by using the phenomenon of EGFR inhibition is found to be an attractive approach that led to magnify the importance of Erbb1 inhibitor. These inhibitors along with their use in clinical processes, are also concerned with the survival of patients and different EGFR antagonists and agonists are also in use for the revelation of various other cascades and the effects of EGFR pathway on them. EGFR inhibitors can be obtained from any relevant supplier at a very normal cost. [Read the Full Post]

PAZOPANIB: LATEST VEGFR INHIBITOR

3684 | Sep 11 2012

PAZOPANIB: A very famous pharmaceutical company named GlaxoSmithKline is the manufacturer of a very important anticancer drug Pazopanib Votrient also called Pazopanib VEGFR inhibitor and is selling it by the market name Votrient. Pazopanib is a quick source of anti-angiogenic activity that inhibits VEGF, R1, VEGFR2 and VEGFR3 in conjunction with the β subtypes and c-kit RTKs and PDGFR-a. Pazopanib is such a tiny structure that got fame only in previous years by showing its remarkable activity in various sorts of cancers. Pazopanib VEGFR-PDGFR inhibitor is indeed one amongst those necessary inhibitors that are currently approved for the utilization at clinical level [1]. Pazopanib structure reveals the presence of a sulfonamide group. One can purchase Pazopanib from supplier Pazopanib by paying Pazopanib price that is around $100 per a 25mg packing under the market name Votrient or GW786034. Its price might vary among the suppliers. Pazopanib solubility is ideally detected in DMSO however it is fully insoluble in water and ethanol. It is stability is increased for nearly 2 years if preserved at -20oC. The studies revealed that Pazopanib IC50 value for VEGF-R1 is 10nM, for VEGF-R2 is 30nM and for VEGF-R3 is 47 nM. Pazopanib IC50 values for few related kinases for example PDFGR-beta is 82 nM, c-fms is 146 nM, c-kit is 74 nM and FGFR1 is 140 nM. [Read the Full Post]

DASATINIB; An Inhibitor of Receptor Tyrosine Kinase

0 | Sep 06 2012

CHARACTERISTICS OF DASATINIB Experts and also scientists are trying hard to find improve drug that will be able to possess efficiency as against cancer which has become responsible of heavy death all over the world and also resistance towards the available drugs in cancer cells is also motivating scientists. Cancer cells avoid both the action of particular medicine by mutating themselves in a number of steps. Metastasis is actually also other problem related to disease. For chemotherapy of disease cell toxicity increases the problem. To attack these afore mentioned errors the only key to combat it to be able to devise new medication. Imatinib was used for many years but toxicity and other consequences mentioned above it obligate scientists to develop one less harmful and more efficient prescription. So in this respect Jagabandhu Das developed one medicine known as Dasatinib. Dasatinib BMS 354825 got very popular compared to Imatinib because of its less toxicity and more performance. It's developed through a pharmaceutical business Squibb and offered under the trade name on Sprycel. [Read the Full Post]

ERLOTINIB– INHIBITOR OF EGFR

517 | Sep 03 2012

CHARACTERISTICS OF ERLOTINIB Erlotinib is one of the tyrosine kinase inhibitors which is also referred OSI-420 EGFR inhibitor which is typically named as HCl salt. Epidermal growth factor tyrosine kinase receptor is sometimes seen abnormal in numerous kinds of cancers so that they are being utilized for the anti-cancer therapy. Plenty of new medicines are being created by using a similar approach [1]. Erlotinib structure revealed that it contained 2 quinazoline rings in its structures and it showed to inhibit the EGFR auto phosphorylation which eventually stops the pathway that is involved in the overexpression of genes. Around 18mg/ml in dimethyl sulfoxide (DMSO) is the Erlotinib solubility however it is scarcely soluble in water and ethanol. For inhibition of EGFR 20nM is Erlotinib IC50 [2]. It is readily oxidized therefore care should be taken to extend its shelf life. Approximately $65 per 1000mg is Erlotinib price and any one can get OSI-420 for any kind of purpose under this trade name. [Read the Full Post]

SORAFENIB-AS A MULTIKINASE INHIBITOR

2695 | Aug 30 2012

SORAFENIB: INTRODUCTION For receiving extracellular or intracellular stimulus numerous types of non-receptor and receptor tyrosine kinases are present in cells which are capable of conducting inhibitory and initiatory action on different signalling pathways. Defect of any type in these processes can cause cancer. The kinases which are involved in the over-expression or under expression of gene that are cause of cancer can be used as target for cancer therapy. Different types of kinases are being inhibited by employing only one inhibitor. Due to the involvement of abnormal tyrosine kinase in the development of cancer inhibitors of tyrosine kinases are being developed and studied to use it as for the treatment of cancer. Clinical trials of different inhibitors have shown outstanding results. Among these inhibitors one important inhibitor is Sorafenib inhibitor which has shown to inhibit kinases excluding respective VEGFR. Similarly Raf pathway/ERK/MEK pathway have been found inhibited by the administration of Sorafenib Raf inhibitor. [Read the Full Post]

EGFR INHIBITORS IN CANCER THERAPY

5239 | Aug 17 2012

EGFR AND DEVELOPMENT OF CANCER: Among a variety of signal transduction pathways vital for cell survival, growth, and proliferation etc. EGFR pathway is considered to be quite important. Its importance has been judged by analyzing the processes like tumor development and some other diseases occurring due to uncontrolled growth of cells. Mostly EGFR signaling pathway malfunctioning has been linked with the development of such types of diseases in the body for example; colon cancer, breast and lung cancer and with anal cancer, multiform Glioblastoma and epithelial cancer. Therefore targeting EGFR for cancer therapy is a feasible approach. This EGFR inhibiting strategy magnifies the HER-1inhibitor and its importance. These inhibitors have a very significant role in the patients’ survival from the disease. Different EGFR agonists and antagonists are used for the purpose of unveiling the role of this molecule in the cell as well as looking for a most efficient EGFR inhibitor. These inhibitors are available at a very reasonable price and can be bought for any purpose. [Read the Full Post]

EGFR INHIBITORS AGAINST TUMORS

4695 | Jul 29 2012

EGFR INHIBITION: There are few pathways which play important roles in the cellular functioning and among these EGFR (epidermal growth factor receptor) pathway is one which is vital for the cell growth, proliferation and survival. The significance of this pathway can only be understood by the formation of cancers and fatal diseases associated with uncontrolled growth of cells due to dysregulation of EGFR signaling pathway. Mutated or over expression of EGFR is linked with many types of cancers for example breast, colon and lung cancers and also with glioblastoma multiform, epithelial and anal cancers. Therefore an attractive strategy to treat cancers was EGFR inhibition by using EGFR inhibitors. In addition to this use in clinics these are also involved in patient survival and various EGFR agonists and antagonists are also being used for the elucidation of different other pathways and effects of EGFR signaling pathway on them. These inhibitors are available at normal prices from any of the relevant supplier. [Read the Full Post]

NILOTINIB AND PHILADELPHIA

6299 | Jul 25 2012

CML AND PHILADELPHIA CHROMOSOME During meiosis the fusion of two genes including BCR a breakpoint cluster and ABL tyrosine kinase results in the formation of Philadelphia chromosome. The resultant fusion protein expressed due to Philadelphia chromosome is not controlled and function abnormally leading to an oncoprotein. Chronic myelogenous leukemia or CML is caused by this fusion oncoprotein in 90% of the patients of CML. Due to huge part of this protein in CML, in drug development for cancer treatment this protein is being targeted by researchers by the help of small molecule screening. Nilotinib AMN-107 is one of the inhibitor used for this purpose to cure CML. [Read the Full Post]

PAZOPANIB: INTRODUCTION

4297 | Jul 19 2012

PAZOPANIB: INTRODUCTION One of the very important anti-tumor drugs Pazopanib VEGFR inhibitor also known as Pazopanib Votrient is being produced by the very popular pharmaceutical company which is GlaxoSmithKline. It is selling this drug with commercial name of Votrient. Pazopanib inhibits the angiogenesis by blocking VEGF R1, R2 and R3 with their β subtypes and also inhibits c-kit RTKs as well as PDGFR-a. Though Pazopanib is tiny molecule yet it gains popularity due to its extensive potential on various kinds of malignancies. Pazopanib VEGFR-PDGFR inhibitor has now been approved to enter the clinical trials. It was revealed by the Pazopanib structure that it contained a sulfonamide group. It is marketed in 25mg of packaging with Pazopanib price of approximately $100 as Votrient or GW786034 and anyone can purchase Pazopanib for research or experimental purposes from supplier Pazopanib. Prices are being varied from supplier to supplier. Pazopanib solubility revealed it is best soluble in DMSO while it is absolutely insoluble in water and ethanol. Storing at -20oC shows stability for approximately 2 years. [Read the Full Post]

NILOTINIB 

6967 | Jul 12 2012

ASSOCIATION OF PHILADELPHIA CHROMOSOME WITH CHRONIC MYELOGENOUS LEUKEMIA Philadelphia chromosome is composed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome promotes fusion protein that functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

GEFITINIB; A POTENT INHIBITOR OF EGFR

606 | Jul 11 2012

INTRODUCTION AND MECHANISM OF ACTION There are many inhibitors of tyrosine kinase inhibitors and amongst these Gefitinib is one of the potent inhibitor. It gently inhibits the functions of EGFR or epidermal growth factor receptor. Currently there are two companies are producing Gefitinib including Astra Zeneca Company and Teva Company. Gefitinib Iressa performs its functions by inhibiting EGFR due to its structural properties which contains a ring structure of anilinoquinazoline. Gefitinib EGFR inhibitor costs around 80$ for a vial of 1g and it is available for anyone desired to purchase Gefitinib including researchers, scientists and for laboratory uses. Gefitinib is not soluble in water however Gefitinib solubility can be attained in ethanol, dimethyl sulfoxide (DMSO) and DMF. As far Gefitinib stability is concerned it is stable for a period of 2 years if stored at -20oC. Gefitinib IC50 is 37nM and 57nM for Tyr 1173 and Try 992 respectively. There were many assays were performed for the pharmacokinetics and sensitivity evaluation of Gefitinib. These assays were based on the information of some presumptive markers such as mutated forms of K-Ras and EGFR and variable copy number. Enzyme linked immunosorbent assay (ELISA) is carried out to analyze human serum and study of tissues against a specific drugs or HDRA. This is a competitor inhibitor of EGFR which competes with ATP and binds with ATP binding site present in EGFR which ultimately results in the inhibition of ligand binding and therefore inhibits the signal transduction which is caused by ligand binding. [Read the Full Post]

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

11948 | Jul 04 2012

CHARACTERISTICS OF DASATINIB The amplified death rate because of cancer and multidrug resistance development in cancer cells for existing drugs are the persuasive force for the researchers as well as scientists to explore new drugs that have better efficiency. Each cellular system is organized by a diversity of controllers called cell cycle regulatory proteins.Cancer cells have the capability to mutate themselves in a variety of ways which make them to detour the action of a specific drug. Another concern with the cancer is that it metastasizes. Other difficulty with the chemotherapy of cancerous cells is toxicity. So considering afore mentioned problems it is evident and compulsory to search for new drugs. Due to above mentioned problematic effects of Imatinib which has been administered for years induces scientists to search for a more mild and more active drug. In this matter a new drug called Dasatinib was discovered by Jagabandhu Das. In contrast to Imatinib, Dasatinib BMS 354825 became renowned due to its lesser harmful and more efficient nature. This drug was discovered by Squibb Company and it is sold as Sprycel. [Read the Full Post]

NILOTINIB

5847 | Jul 05 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]

NILOTINIB

6704 | Jun 28 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]

SORAFENIB- A MULTIKINASE TYROSINE INHIBITOR

3597 | Jun 27 2012

SORAFENIB: INTRODUCTION Various kinds of non-receptor tyrosine kinases or receptor tyrosine kinases (RTKs) are available in the cells which are employed in responding to intra or extracellular stimulusby carrying out either initiatory or inhibitory action on various signaling pathways. Any sort of problem in this process may cause cancer. Inhibition of kinase enzymes to prevent some mal-expressed or over-expressed gene causing cancer is found to be an effective tool. Inhibition of various kinases is being done by using single inhibitor. Since malfunctioned tyrosine kinases are involved in onset of cancer, research is being done on their inhibitors for cancer therapy.Many of them are giving promising results in their clinical trials.An important example of these inhibiting drugs is Sorafenib VEGFR inhibitor that has been found to inhibit the protein kinases except respective VEGFR. When SorafenibRaf inhibitor was given Raf/MEK/ERK pathway was found inhibited. [Read the Full Post]

DASATINIB; A Receptor Tyrosine Kinase inhibitor

4604 | Jun 25 2012

PROPERTIES OF DASATINIB Researchers and scientists are trying hard to find a better drug with good efficiency because cancer has become the cause of huge deaths all over the world and secondly resistance to the available drugs in cancer cells is increased. Cancer cells evade the action of particular medicine to become resistant by mutating themselves in a number of ways. Metastasis is also another problem related to cancer. For chemotherapy of cancer cell toxicity adds to the problem. To combat these afore mentioned difficulties it is necessary as well as mandatory to devise new medicines. Imatinib was given for years but due to its toxicity and other effects mentioned above it forced scientists to develop a less toxic and more efficient medicine. So in this regard Jagabandhu Das developed a new medicine called Dasatinib. Dasatinib BMS 354825 got very popular as compared to Imatinib because of its lesser toxicity and more efficiency.It is developed by a pharmaceutical company Squibb and marketed under the trade name of Sprycel. [Read the Full Post]

ERLOTINIB– THE HCL SALT

5715 | Jun 19 2012

ERLOTINIB AND ITS PROPERTIES Erlotinib comes under the category of tyrosine kinase inhibitorswhich is also called OSI-420 EGFR inhibitor and usually named as HCl salt. Epidermal growth factor tyrosine kinase receptor is usually seen abnormal in various types of cancers so they are being employed for the anti-cancer therapy. A lot of new medicines are being produced by using the same approach [1]. Erlotinib structure revealed that it contained two quinazoline rings in its structures and it showed to inhibit the EGFR auto phosphorylationwhich eventually stops the pathway which is involved in the overexpression of genes. Around 18mg/ml in dimethyl sulfoxide (DMSO) is the Erlotinib solubility however it is scarcely soluble in water and ethanol. For inhibition of EGFR 20nM is Erlotinib IC50 [2]. It is easily oxidize able so care must be taken to increase its shelf life. Approximately $65 per 1000mg is Erlotinib price and buy OSI-420 for any kind of purpose under this trade name. [Read the Full Post]

SUNITINIB-AN RTK INHIBITOR

3478 | Jun 17 2012

MULTIKINASE INHIBITORS AND CHEMOTHERAPY A variety of cell signalling pathways are there in the cellular systems of the body that govern different cellular processes in the cells. Tyrosine kinase pathways are one of these pathways that play role in growth, proliferation, survival and apoptosis etc. Overexpressed tyrosine kinases may hence lead to cancer and is amongst the major reasons in most of the cancer conditions. Inhibition of tyrosine kinases is hence being done by using different types of tyrosine kinase inhibitors. A single inhibitor may sometimes block multiple kinases in one time. The examples of cancers involving tyrosine kinase defects is breast cancer in which VEGF pathway is disturbed. Various kinds of carcinomas involving such defects are being treated using these tyrosine kinase inhibitors for example gastrointestinal stromal tumors and Acute Lymphoblastic Leukaemia (ALL).  [Read the Full Post]

NILOTINIB AND PH+

6512 | Jun 10 2012

PHILADELPHIA CHROMOSOME AND CML Philadelphia chromosome is formed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome gives rise to a fusion protein that is functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

SORAFENIB-AS A MULTIKINASE INHIBITOR

3664 | Jun 08 2012

SORAFENIB For receiving extracellular or intracellular stimulus numerous types of non-receptor and receptor tyrosine kinases are present in cells which are capable of conducting inhibitory and initiatory action on different signalling pathways. Defect of any type in these processes can cause cancer. The kinases which are involved in the over-expression or under expression of gene that are cause of cancer can be used as target for cancer therapy. Different types of kinases are being inhibited by employing only one inhibitor. Due to the involvement of abnormal tyrosine kinase in the development of cancer inhibitors of tyrosine kinases are being developed and studied to use it as for the treatment of cancer. Clinical trials of different inhibitors have shown outstanding results. Among these inhibitors one important inhibitor is Sorafenib inhibitor which has shown to inhibit kinases excluding respective VEGFR. Similarly Raf pathway/ERK/MEK pathway have been found inhibited by the administration of Sorafenib Raf inhibitor. [Read the Full Post]

PAZOPANIB: LATEST VEGFR INHIBITOR

3938 | Jun 06 2012

PAZOPANIB: INTRODUCTION One of the very important anti-tumor drugs Pazopanib VEGFR inhibitor also known as Pazopanib Votrient is being produced by the very popular pharmaceutical company which is GlaxoSmithKline. It is selling this drug with commercial name of Votrient. Pazopanib inhibits the angiogenesis by blocking VEGF R1, R2 and R3 with their β subtypes and also inhibits c-kit RTKs as well as PDGFR-a. Though Pazopanib is tiny molecule yet it gains popularity due to its extensive potential on various kinds of malignancies. PazopanibVEGFR-PDGFR inhibitor has now been approved to enter the clinical trials. It was revealed by the Pazopanib structure that it contained a sulfonamide group. It is marketed in 25mg of packaging with Pazopanib price of approximately $100 as Votrient or GW786034 and anyone can buy Pazopanib for research or experimental purposes from supplier Pazopanib. Prices are being varied from supplier to supplier. Pazopanib solubility revealed it is best soluble in DMSO while it is absolutely insoluble in water and ethanol. [Read the Full Post]

DASATINIB- A DRUG OF CHOICE

7022 | Jun 04 2012

INTRODUCTION Diverse types of cellular systems are there in human bodies that differ structurally and functionally from one another. Each cellular system is controlled by a variety of controllers called cell cycle regulatory proteins. Defective controllers may lead to abnormal cellular systems and the condition known as cancer may develop. Cancer may be of different types depending upon the defect in the cell cycle regulatory proteins. Cancer may also vary on the basis of stage of the defective condition. Many therapies have been devised in order to treat cancerous cells. Further research is also being done for developing better, more specific and less toxic therapies and to cope with the development of resistance in the defective cells against existing therapies. Besides resistance, metastasis is also another issue to be resolved in case of cancerous cells. Imatinib has been used against leukemia for several years but due to high levels of toxicity scientists discovered a new drug, called Dasatinib, for the same therapy. Dasatinib BMS-354825 is more efficient and less toxic as compared to Imatinib. The drug is being marketed by the name of Sprycel. As Dasatinib was discovered by Jagabandhu Das, it was named Dasatinib. Development of the drug was done by Squibb Company. [Read the Full Post]

NILOTINIB

6866 | May 30 2012

ROLE OF BCR-ABL TYROSINE KINASES IN CML: A chimeric BCR-ABL oncogene is obtained by the fusion of Abelson (ABL) tyrosine kinase (TK) gene and break-point cluster (BCR) gene, and here TK has been related to pathogenesis of CML (Chronic Myelogenous Leukemia), 90% of this debilitating disease involves chromosomal abnormalities leading to formation of so-called Philadelphia chromosome. As there is a confirmed participation of BCR-ABL TK in PH+ CML, different inhibitors that target this TK have registered remarkable success in treatment of CML and among them Nilotinib bcr-abl inhibitor is the most valuable one. It is a form of tyrosine kinase inhibitor and is a hydrochloride monohydrate salt. [Read the Full Post]

GEFITINIB; AN EGFR INHIBITOR

4885 | May 28 2012

PROPERTIES AND MODE OF ACTION Gefitinib is one of several tyrosine kinase inhibitors that are quite efficient in their activity. Gefitinib is actually an EGFR inhibitor. It is marketed by the two companies i.e., Teva and AstraZeneca. Gefitinib EGFR inhibitor is a strong inhibitory compound and Gefitinib structure shows the presence of a ring in it i.e., anilinoquinazoline. One can buy Gefitinib in the form of a 1 gm vial in approximately $80. Scientists can purchase Gefitinib for research or treatment purposes. Gefitinib solubility can be achieved in organic solvents like ethanol, DMSO and DMF and Gefitinib stability for approximately 2 years can be achieved if it is stored at -20 oC. Gefitinib IC50 for EGFR inhibition against Tyr 992 and Tyr 1173 is 37 nM and 57 nM respectively. Different types of assays have been designed to clinically analyze the pharmacokinetics and sensitivity of the drug. These assays are based upon some predicting markers e.g., EGFR mutated genes, copy number or K-Ras mutations. [Read the Full Post]

SUNITINIB: A MULTI-KINASE ENZYME INHIBITOR

4000 | May 24 2012

TYROSINE KINASE INHIBITORS Tyrosine kinase enzymes are very important amongst the diversified world of proteins involving the signal transduction process for their role in various processes like inhibition or activation of genes expression responsible for cell growth, cell division, cell differentiation and cell death. Abnormalities in these tyrosine kinases are leading cause of in the disruption in above mentioned functions stimulating the tumor development. The inhibition of tyrosine kinase enzyme is an attractive target when there is the disruption in any cell cycle regulatory enzyme affected by the tyrosine kinase in case of any kind of cancer. So these enzymes are the attractive target for anti-tumor drugs as they are those that start the function. Tyrosine kinase inhibitors are having the ability of affecting different kinds of tyrosine kinase enzymes hence called as multikinase inhibitors and they may be non-receptor or receptor kinases. If the type of kinase involving in the cancer condition is known, like for VEGF involved in the breast cancer, the medicine for choice must be a TKI. [Read the Full Post]

SUNITINIB: THE MULTI-TARGETED APPROACH

3748 | May 23 2012

MUTIKINASE INHIBITORS IN CHEMOTHERAPEUTICS: Tyrosine kinases are the enzymes which act as mediators between different cells to facilitate variety of metabolic processes in the cells. The inhibition of these enzymes is found to be a very attractive target due to their prime role in various important processes in the cells for instance cellular growth, survival, proliferation, apoptosis and differentiation. Any type of modulation of these enzymes can cause the downstream regulation of the pathways controlled by them. This is why inhibitors to tyrosine kinases are getting very famous as chemotherapeutic agents. Many tyrosine kinase inhibitors are multikinase inhibitors as they can inhibit more than one type of tyrosine kinase enzymes. VEGF pathway involvement in breast carcinoma and some other tyrosine kinases in other cancers made these enzymes a popular interest. Tyrosine kinase inhibitors are used successfully against solid form tumors and various multi tyrosine kinase inhibitors are used for treating gastrointestinal stromal tumors. Tyrosine kinase inhibitors are also employed for the treatment against acute form of lymphoblastic leukemia. [Read the Full Post]

PAZOPANIB: LATEST VEGFR INHIBITOR

3652 | May 22 2012

PAZOPANIB: INTRODUCTION A very famous pharmaceutical company named GlaxoSmithKline is the manufacturer of an important anticancer drug Pazopanib Votrient known as Pazopanib VEGFR inhibitor and is selling it under the trade name Votrient. Pazopanib is a good source of anti-angiogenic activity that inhibits VEGF, R1, VEGFR2 and VEGFR3 along with the β subtypes and c-kit RTKs and PDGFR-a. Pazopanib is a very small molecule that got fame in just in recent years by exhibiting its potential activity in case of different types of cancers. PazopanibVEGFR-PDGFR inhibitor is indeed one of those important inhibitors which are now approved for the use at clinical level [1]. Pazopanib structure reveals the presence of a sulfonamide group. One can buy Pazopanib from supplier Pazopanib by paying Pazopanib price that is around $100 per a 25 mg packing under the trade name Votrient or GW786034. Its price may vary among the suppliers. Pazopanib solubility is best observed in DMSO but it is completely insoluble in ethanol and water. It is stable for almost two years if stored at -20oC. [Read the Full Post]

SORAFENIB-AS A MULTIKINASE INHIBITOR

3230 | May 21 2012

SORAFENIB Various kinds of receptor and non-receptor kinase enzymes are there in the cells that are responsible of carrying out the signaling pathways of initiation or inhibition of cascades after getting intra or extracellular stimulus. Any sort of defect in this process may cause cancer. Inhibition of kinase enzymes to prevent some mal-expressed or over-expressed gene causing tumor is found to be an effective approach. Many multiple kinases can be inhibited by using a single inhibitor. Various types of inhibitors against these kinase proteins are being discovered and studied in order to develop some effective anti-cancer therapy, as many of the tyrosine kinase abnormalities used to become the cause of development of cancer. Many of them are giving promising results in their clinical trials. An important example of these inhibiting drugs is Sorafenib VEGFR inhibitor that has been found to inhibit the protein kinases except respective VEGFR. In the same way Sorafenib Raf inhibitor also an important drug used for the inhibition of MEK/ERK/Raf pathway. [Read the Full Post]

DASATINIB; AN ANTI-RTK DRUG

4576 | May 16 2012

DASATINIB AND ITS PROPERTIES The high rate of deaths due to cancer and the development of resistance in the cancerous cells for existing drugs are encouraging the scientists and researchers to look for more efficient drugs. Occurrence of different types of mutations makes the cancerous cells to evade the drugs’ action against them. Metastasis is another problem in cancer that complicates the issue. Toxicity is another that is raised in cancer chemotherapy, therefore considering all of the developing complexities, new drugs are quite necessary to be discovered and developed. In case of leukemia, Imatinib had been used since long but due to the complexities associated with this drug, as mentioned above, led the scientists to look for another less toxic and more efficient drug. Jagabandhu Das was the discoverer of a drug in this regards i.e., Dasatinib named so after its discoverer. Dasatinib BMS 354825 got very popular because of lesser toxicity and more efficacies as compared to that of imatinib. It was developed by the company Squibb and is sold under the name of Sprycel. [Read the Full Post]

PAZOPANIB – THE LATEST CLINICAL VEGFR INHIBITOR

3006 | May 10 2012

PAZOPANIB: INTRODUCTION Pazopanib VEGFR inhibitor is compound manufactured by a famous pharmacuetical company GlaxoSmithKline under the trading name of Votrient, is a potential source of anti-angiogenic activity which inhibits R1, VEGF, VEGF R3 and VEGF R2 along with β subtypes and PDGFR-a and c-kit RTKs. Pazopanib is a small molecule which got famous in recent years when it showed potential activity in various types of tumors. PazopanibVEGFR-PDGFR inhibitor is actually one of those few inhibitor molecules that are approved for their use at clinical levels. Its structure revealed the presence of sulfonamide group in it. One can purchase Pazopanib to supplier Pazopanib under the trading name Votrient or GW786034 by paying the price around $100 for a 25 mg vial. Pazopanib price may vary from supplier to supplier. Pazopanib solubility is very good in DMSO but not in water and ethanol. Its stability is for almost 2 years when stored at -20oC. Pazopanib IC50 for efficient VEGF R1, VEGF -2, VEGF -3 inhibitions is actually 10 nM, 30nM and 47 nM respectively. For closely related kinase enzymes for example PDGFR-FGF R1, c-Kit and c-fms, Pazopanib IC50 was recorded as 85 nM, 140 nM, 74 nM and 146 nM, respectively. [Read the Full Post]

IMATINIB – INHIBITS MULTIPLE KINASES

6007 | May 07 2012

INTRODUCTION: SRC inhibitors are the molecules specific for targeting the non rector tyrosine kinase enzymes of SRC family and have the potential of inhibiting the 2 or more members of two SRC subfamilies, Fyn, Src. Fgr, Yes, Lck, Blk, Frk and Hck SRC kinases. These kinase enzymes take part in various pathways, so targeting them has became an attractive and valuable approach in the field of chemotherapy. Imatinib is commonly known as STI-571. Imatinib SRC inhibitor is a molecule originally named as STI571 and marketed by the company Novartis in the form of its mesylate salt hence known as STI-571 Imatinib Mesylate. This salt form is especially developed for targeting the cancer cells sparing the normal cells from them hence developed as personalized drug. [Read the Full Post]

GEFITINIB – EGFR REGULATING DRUG FOR LUNG CANCER

4462 | May 02 2012

GEFITINIB: PROPERTIES AND MECHANISM OF ACTION There are two companies that are marketing Gefitinib named AstraZeneca and Teva. Gefitinib drug is actually Gefitinib EGFR inhibitor molecule that is an efficient and strong compound and has undergone clinical trials. Gefitinib structure reveals that a ring of anilinoquinazoline is present in it. Gefitinib price for a 1 gram vial is around $80 and due to its reasonable price one can purchase Gefitinib EGFR inhibitor very easily for laboratory or research purposes from any supplier Gefitinib. Gefitinib stability is for almost 2 years if stored at -20 degrees. To inhibit Tyr 1173 and Tyr 992 properly, the Gefitinib IC50 is found to be 57 nM and 37 nM respectively for inhibition of EGFR. Various Gefitinib assays were carried out to check the sensitivity and pharmacokinetic properties of this drug and those clinical assays were found to base upon some certain predictive markers like EGFR mutated genes, mutations in K-Ras and copy number. [Read the Full Post]

ERLOTINIB (OSI-420) –A SALT OF HCL

3902 | May 01 2012

INTRODUCTION: Erlotinib drug is commonly known as HCl salt. It is also called as OSI-420 EGFR inhibitor. It is a small molecule of tyrosine kinase inhibitor that works against the receptor for epidermal growth factor. This epidermal growth factor results usually very high levels of expression and mostly gets mutated in case of various types of tumors, hence a valuable and attractive target for anti-tumor therapy. One can order OSI-420 to any of the supplier OSI-420. So one can purchase OSI-420 by paying Erlotinib price to its supplier that is around $65 for 1000 mg vial. Erlotinib structure describes that it has 2 rings of quinazoline. OSI-420 has found to be inhibiting the autophosphorylation of epidermal growth factor to render downstreaming of already stopped signaling cascade by binding to ATP binding site of EGFR in the reversible manner leading to a permanat change in its conformation or structure. Erlotinib solubility is 18 mg/ml in DMSO while it is very poorly soluble in water and ethanol. To inhibit EGFR tyrosine kinase enzyme in human, Erlotinib IC50 was found to be almost 20 nM. OSI-420 EGFR inhibitor must be kept far away from different oxidizing agents so that it will remain stable and safe. [Read the Full Post]

DASATINIB: A DOUBLE-EDGED SWORD

3138 | Apr 25 2012

The demand for advance and innovative therapeutic tools has always been in high level for the efficient treatment of various kinds of cancers. The cancers that are highly proliferative and metastatic in nature have put an additional stress on the designing and discovery of a medicine or drug which promises better results. Mostly they adapt such mutations which tend them to remain unaffected to further treatment as a result evading the effects of drugs targeting them. High level toxicity is another big problem related to chemotherapy. For the treatment of blood cancer, Imatanib is found to be the best example of above mentioned statement. The reason that lead to the discovery of a better, less toxic and an efficient drug for treating white blood cell cancer is actually the resistance developed against Imatinib in the leukemic cell lines and its higher level of toxicity. [Read the Full Post]

SORAFENIB-A MULTIKINASE INHIBITOR

2704 | Apr 24 2012

SORAFENB Different types of receptor or non-receptor kinases are there in the cells that are involved in the signaling process in order initiate or inhibit a process after getting extra/intracellular stimulus. Any defect in this system may lead to cancer. Inhibition of Kinases in order to prevent any over-expressed or mal-expressed gene causing cancer is a very effective strategy. There are multiple types of kinases which can be inhibited by a single type of inhibitor. As various Tyrosine kinase aberrations become the reason for developing cancers, many inhibitors against these proteins are being researched in search of developing an effective anti-cancer therapy. Any of them are undergoing clinical trials and are giving promising results. One of the examples of such inhibitors is Sorafenib VEGFR inhibitor that has also been seen to inhibit protein kinases other than respective VEGFR. Similarly Sorafenib Raf inhibitor may be used effectively for inhibition of MEK/Raf/ERK pathway. [Read the Full Post]

SUNITINIB- A MULTI-KINASE INHIBITOR

2574 | Apr 22 2012

TYROSINE KINASE INHIBITORS Amongst a diversified world of signal transduction proteins, Tyrosine kinase proteins are important due to their role in different processes like activation or inhibition of expression of genes involved in growth, cell division, differentiation and cell death. Aberrations in any of such tyrosine kinases may lead to disruption in any of the above mentioned function and may develop tumor. In any type of cancer where any of the cell cycle regulatory protein that is affected by tyrosine kinases is disturbed, inhibition of Tyrosine kinases may work well to cope with the condition. They are attractive targets for anti-cancer drugs as they are the ones that start the activity. TKIs (Tyrosine Kinase Inhibitors) may affect different types of Tyrosine kinases, therefore are called as multikinase inhibitors they may be receptor or non-receptor tyrosine kinases. If we know the type of kinase involved in the cancerous condition, e.g., if VEGF involved in breast cancer, the drug of choice is definitely a TKI. [Read the Full Post]

DASATINIB- A MULTI ACTION INHIBITOR

3079 | Apr 15 2012

Cancer has always been an area of research that has got much attention due to its diversity in reasons and mechanisms and hence to look for the treatment. Metastasis is another challenge that has to be controlled over in order to get rid of this disease completely. Due to this diversity every single treatment does not necessarily suits every single cancer patient. Therefore it is need of the hour to discover and synthesize new and more effective drugs with lesser toxicity as occurs in different chemotherapeutic agents for example in case of leukemia, Imatinib is a very good example. Toxicity of Imatinib at high level led the scientists to discover a new drug named Dasatinib. Dasatinib BMS-354825 is comparatively efficient and is less toxic. It is sold under the trade name of Sprycel. Dasatinib has been named on the name of the inventor Jagabandhu Das and was developed by Squibb. [Read the Full Post]

GEFITINIB – EGFR REGULATOR IN LUNG CANCER

3478 | Apr 12 2012

PROPERTIES OF GEFITINIB AND MECHANISM OF ACTION: Teva and AstraZeneca are the manufacturing and marketing companies of Gefitinib. Gefitinib EGFR (HER) inhibitor is a strong and efficient compound that has undergone clinical evaluations. An anilinoquinazoline ring is present in the structure of Gefitinib. For a 1 gram package the price for Gefitinib is about $80 due to this reasonable cost its easier to buy Gefitinib. If someone wants to order Gefitinib for research or laboratory uses one can contact any of Gefitinib suppliers. It can be stable for 2 years if properly stored at -20 oC. For proper inhibition of Tyr992and Tyr1173 Gefitinib IC50 is 57nM and 37nM respectively for EGFR inhibition. Different Gefitinib assays are done to analyze the pharmacokinetics, sensitivity and effect of this agent and those assays were based on certain predictive markers such as EGFR mutated gene, K-Ras mutations and copy number. In routine researchers use HDRA (histoculture drug response assay) or ELISA (enzyme linked immunosorbent assay) of human serum in order to analyze its pharmacokinetics studies. The mechanism behind the actions of Gefitinib is the binding of this compound competitively with EGFR ATP-binding site in cancer cells surface hence resulting in the inhibition of EGFR tyrosine phosphorylation induced by ligand to check downstream pathways. [Read the Full Post]

LINIFANIB-A FIRST LINE INHIBITOR AGAINST CANCER

4090 | Apr 11 2012

RECEPTOR TYROSINE KINASES AND CANCER Receptor tyrosine kinases (RTKs) are transmembrane receptors that start signaling cascade inside the cell after getting stimulated by different types of respective ligands. The stimulation may arise from the immediate or far away surroundings of the cell. Actually they respond to the needs of their extracellular environment by stimulating or inhibiting different types of cellular activities of regulation of cell cycle e.g., expressing or inhibiting a gene. After getting stimulated they phosphorylate themselves, dimerize and initiate a signaling cascade in multiple dimensions showing amplified effect of a single ligand. As these receptors have multiple types of effects therefore any change in their structure might lead to a gross change in the activities and behavior of the cell. As they are cell cycle regulatory proteins there over or under expression may lead to different types of diseases like cancer. [Read the Full Post]

NILOTINIB

4422 | Apr 08 2012

ROLE OF BCR-ABL IN CML BCR (break-point cluster) and (ABL) Abelson genes code for the protein tyrosine kinases that are involved in signal transduction fusion of these two genes occur when a philadalphia chromosome is formed after some mistake in the process of crossing over. This chimeric oncogene is known as BCR-ABL and is known to be involved in the development of leukemia especially (CML) Chronic Myelogenous Leukemia. This type of fusion is known to be responsible for almost 90% CML cases and is known as PH+ CML. The participation of BCR-ABL in PH+ CML has urged the scientists to inhibit this fusion protein. Different types of inhibitors targeting this oncogenic fusion protein have been registered. Nilotinib Src-bcr-Abl inhibitor is one of such inhibitors against CML. [Read the Full Post]

FINGOLIMOD – AN IMMUNOMODULATOR

3045 | Apr 02 2012

PROPERTIES AND ORIGIN: Fingolimod (FTY720) derivative of a metabolite of a fungal strain Isaria sinclairii,and is known to be the 1st oral medicine which recently get approval for using against the multiple Sclerosis. Multiple seclerosis is an auto immune disease hence Fingolimod offers a glimmering hope against this debilitating disease. Fingolimod got approval in 2010-11 and after its approval Novartis (manufacturers) ensured its continous availability in market for patients. structure of Fingolimod SIP receptor inhibitor is chemically very different from ISP-1 (parent metabolite) and in order to enhance its efficacy and phamacokinetic properties, this sphingosine analog molecule is rationally modified. This drug is marketed by name Fingolimod Gilenya. This drug is an immunomodulating one and was used as an anti-rejection drug after the transplantation processes in clinical trials of phase I and phase II. [Read the Full Post]

ERLOTINIB (OSI-420) – AN HCL SALT

3605 | Apr 02 2012

INTRODUCTION: Erlotinib is commonly known as Erlotinib salt of HCl. It is a very small tyrosine kinase inhibitor molecule, works against the epidermal growth factor receptor. This EGFR usually gives high level of expression and most often gets mutated in different types of cancers, hence an attractive target for the anti-cancer therapy. Researchers can purchase Erlotinib from supplier Erlotinib which sale it under the trading name of Tarceva. By paying Erlotinib prices around $65 for a 1000 mg vial one can buy OSI-420. Structure of Erlotinib reveals that it is having 2 rings of quinazoline. Erlotinib has found to inhibit the autophosphorylation of EGFR to render the downstreaming of stopped signaling pathway by binding to the ATP binding region of EGFR in a reversible manner causing a permanent conformational change in its structure. Erlotinib is poorly soluble in ethanol and water but gives a solution of 18 mg/ml upon heating in DMSO. For the inhibition of EGFR tyrosine kinase in human, Erlotinib IC50 is found to be near 20 nM. Erlotinib must be stored far away from oxidizing agents to keep it safe and stable. [Read the Full Post]

A DOUBLE-EDGED SWORD: DASATINIB

2983 | Mar 29 2012

For the proper treatment of different types of cancers, there has always been a great demand of new and innovative therapeutic options. Those cancers are mostly highly metastatic and proliferative , and this thing puts an additional stress upon the discovery or designing of a drug which gives promising results. They most often develop some mutations which make them unaffected to on-going treatment hence evading the effect of medicines which target them. High toxicity level is another major problem related to chemotherapeutics. Imatanib is one of the prominent examples of above described statement which was in use for the treatment of leukemia. The high level of toxicity and the resistance developed against Imatanib in leukemic cell lines has led to the discovery of another efficient and less toxic drug for treatment of WBC carcinoma. Dasatinib BMS-354825 is such a drug named after its inventor Jagabandhu Das. It enters the horizon of success at this stage hence found to be a good replacement therapeutic agent developed by Squibb for the treatment of cancer and is sold now under the name of brand Sprycel. [Read the Full Post]

LINIFANIB: INHIBITOR FOR RECEPTOR ENZYMES

2940 | Mar 28 2012

LINIFANIB: A MULTIPLE KINASE INHIBITIOR: Receptor tyrosine kinases are the enzymes which are responsible of receiving signals from neighboring cells and extracellular environment so they are mostly the initiating point for the different signaling pathways and hence known as sentry of cells. Due to their importance in different signaling cascades, even very small changes in the activity or structure of RTKs can get magnify in form of differential signaling and leads to an entirely different outcome. In various diseased conditions, especially cancers, different receptor tyrosine kinases are either dysregulated or over expressed and finally lead to target the very first signaling level, which is an attractive approach in anti-tumor therapeutics. Due to their broad spectrum of action, it’s testing and development is very much welcome. Linifanib is a small inhibitor molecule which targets more than one Receptor tyrosine kinase enzymes. The potential anti-cancer property of Linifanib PDGFR inhibitor was discovered when its tumor regression in xenografts of human fibrosarcoma cells HT1080 and in estradiol-induced uterine edema’s model of murine. Synthesis of Linifanib took place as a side product of chemical modification in certain drugs. [Read the Full Post]

PAZOPANIB – A NOVEL VEGFR INHIBITOR FOR CANCER TREATMENT

2556 | Mar 27 2012

PAZOPANIB INTRODUCTION: Pazopanib is a product of GlaxoSmithKilne (GSK) pharmaceutical company and is traded under the name of Votrient, it is an anti-angiogenic chemical compound. Pazopanib VEGFR-PDGFR inhibitor which acts on multiple VEGFR (R1, R2 and R3) and it is also a potent inhibitor of PDGFR’s α and β subtypes and RTK c-kit receptor is also found to be inhibited by Pazopanib. In recent years great potency of this compound has been reported against different tumors and these findings brought fame to this molecule. It is amongst few VEGFR inhibitors which are approved for clinical usage. The structure of Pazopanib contains a sulfonamide group. The Pazopanib price for a vial of 25mg is about $100 but it variability is found from one Pazopanib supplier to other. If someone wants to purchase Pazopanib one can buy Pazopanib by trade name Votrient or GW786034. This compound is soluble in the DMSO and it is stable for atleast two years when stored at -20oC. IC50 for its effective response is 10nM, 30nM and 47 nM for VEGFR1, R2 and R3 respectively. And IC50 for PDGFR-beta FGF R1, c-fims and c-Kit is 84nM, 140nM, 74nM, 146 nM and 140nM respectively. [Read the Full Post]