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JAK/STAT

Fludarabine-PET in a murine model of multiple myeloma

1 | Dec 08 2019

Hovhannisyan N et al. suggested that [18F]fludarabine-PET might represent an alternative and perhaps more specific modality for MM imaging when compared to [18F]FDG. Nevertheless, more investigations are required to extend this conclusion to humans. [Read the Full Post]

Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1

4 | Dec 04 2019

Tang Y et al. demonstrated that decreased expression of Prrx1 stimulates SDF-1/CXCR4 signalling and contributes to organ colonisation with blood CTCs in HCC. STAT3 inhibition and specific blockade of CXCR4 have clinical potential as therapeutics for eliminating organ metastasis in advanced HCC. [Read the Full Post]

The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models

40 | 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]

Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis

74 | 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

64 | 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

54 | 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

95 | 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]

ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy

80 | 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]

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

82 | 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

76 | Aug 15 2019

Zhang J et al. provided a new treatment strategy for patients with EGFR-TKI resistance in NSCLC. [Read the Full Post]

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

131 | 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]

Overcoming Acquired Resistance to AZD9291, A Third-Generation EGFR Inhibitor, through Modulation of MEK/ERK-Dependent Bim and Mcl-1 Degradation

83 | 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]

JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation

117 | 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]

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

116 | 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]

Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells

168 | 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

204 | 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]

Regulation of Skeletal Muscle DRP-1 and FIS-1 Protein Expression by IL-6 Signaling

134 | Jun 03 2019

Fix DK et al. elevated IL-6 can directly induce DRP-1 and FIS-1 expression through gp130 signaling in cultured myotubes and skeletal muscle. Furthermore, ERK 1/2 signaling is necessary for the IL-6 induction of DRP-1 and FIS-1 expression in myotubes. [Read the Full Post]

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial

173 | May 21 2019

Rummel M et al. indicated that in combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. [Read the Full Post]

Thromboembolic events in polycythemia vera

267 | 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

291 | 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]

PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer

170 | Apr 14 2019

Kirschner AN et al. showed that PIM inhibition is a potential treatment for MYC-driven prostate cancers including CRPC, and its effectiveness may be enhanced by activators of the p53 pathway, such as radiation. [Read the Full Post]

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

185 | Apr 11 2019

Hubbard JM et al. showed that napabucasin may prove useful in targeting cancer stem cells, with the potential to suppress metastasis and prevent relapse in patients with varying cancer types. [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]

Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials

261 | 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

287 | 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]

Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds

836 | 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]

The thrombopoietin/MPL axis is activated in the Gata1low mouse model of myelofibrosis and is associated with a defective RPS14 signature

507 | 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

503 | 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

2247 | 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]

JAK2 inhibitor CEP-33779 prevents mouse oocyte maturation in vitro

541 | Nov 15 2018

Wu C et al. suggested that JAK2 regulated the microfilaments aggregation during the mouse oocyte maturation. [Read the Full Post]

Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduce mitochondrial ROS production

355 | Nov 03 2018

Meier JA et al. outlined a role for mitochondrially localized STAT3 in sensing and responding to external stimuli. [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

462 | 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]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

747 | 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]

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]

JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana

479 | Sep 09 2018

Geng T et al. suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better understand the molecular mechanisms of JAK/STAT signaling pathway in antifungal immune response in silkworm. [Read the Full Post]

microRNA-200a silencing protects neural stem cells against cerebral ischemia/reperfusion injury

444 | Sep 09 2018

Ma J et al. indicated miR-200a silencing protects NSCs from OGD/R-induced injury, possibly via regulating the STATs/c-Myc and MAPK/c-Myc signalings. [Read the Full Post]

Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors

723 | 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]

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

0 | Sep 05 2018

Shi L et al. suggested that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. [Read the Full Post]

MicroRNA-17 regulates autophagy to promote hepatic ischemia/reperfusion injury via suppression of signal transductions and activation of transcription-3 expression

453 | Sep 02 2018

Li S et al. showed that high levels of miR-17 expression can function to up-regulate autophagy to aggravate hepatic IRI by suppressing Stat3 expression. Liver Transplantation 22 1697-1709 2016 AASLD. [Read the Full Post]

Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis

912 | 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]

JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

687 | 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

822 | 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]

B7-H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin-6/signal transducer and activator of transcription 3 pathway activation

902 | 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]

EGF-mediated EGFR/ERK signaling pathway promotes germinative cell proliferation in Echinococcus multilocularis that contributes to larval growth and development

1028 | 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]

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases

1073 | 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]

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

808 | May 28 2018

Shi L et al. suggested that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. [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

846 | 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]

Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects

1037 | 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]

Cancer-associated fibroblasts attenuate Cisplatin-induced apoptosis in ovarian cancer cells by promoting STAT3 signaling

649 | Apr 06 2018

Yan H et al. suggested that CAFs could activate the anti-apoptotic STAT3 signaling, thereby decrease the Cisplatin-induced apoptosis and promote chemoresistance in ovarian cancer. [Read the Full Post]

FYN promotes breast cancer progression through epithelial-mesenchymal transition

1337 | 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

1234 | 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]

NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells

1039 | 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

956 | 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]

Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4

893 | 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

2367 | 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]

Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification

1660 | 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]

Tyrosine receptor kinase B is a drug target in astrocytomas

2479 | 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

1259 | 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

1296 | Dec 24 2017

Zhang Y et al. provided novel insights into the mechanism of ErbB2 inhibition by neratinib. [Read the Full Post]

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

1387 | 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]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

881 | Dec 14 2017

Cayrol F et al. showed that the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [Read the Full Post]

Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model

864 | Dec 12 2017

Zhang Y et al. provided a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence. [Read the Full Post]

MET Copy Number Gain Is Associated with Gefitinib Resistance in Leptomeningeal Carcinomatosis of EGFR-mutant Lung Cancer

1525 | 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]

Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447

932 | Dec 02 2017

Peters TL et al. characterized recurrent PIM1 protein-coding mutations found in DLBCL clinical samples and find most preserve the wild-type protein's ability to protect cells from apoptosis but do not bypass activity of PIM447. Pan-PIM inhibition therefore may have an important role to play in the therapy of selected ABC-DLBCL cases. [Read the Full Post]

Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells

1305 | 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]

Quantitative proteomics of breast tumors: Tissue quality assessment to clinical biomarkers

1432 | 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

1631 | 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

1273 | 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]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

2973 | 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]

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

1314 | Oct 04 2017

Song Z et al. suggested that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia. [Read the Full Post]

Regulation of TRPM7 Function by IL-6 through the JAK2-STAT3 Signaling Pathway

940 | Sep 05 2017

Liu A et al. indicated IL-6 inhibits the inward TRPM7 current via the JAK2-STAT3 signaling pathway. [Read the Full Post]

Oncogene swap as a novel mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor in lung cancer

1397 | 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]

Interleukin 6 induces cell proliferation of clear cell renal cell carcinoma by suppressing hepaCAM via the STAT3-dependent up-regulation of DNMT1 or DNMT3b

1273 | Aug 17 2017

Quan Z et al. provided a novel signal pathway regulating cell proliferation, potentially representing a therapeutic target for RCC. [Read the Full Post]

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

1256 | Aug 17 2017

Dai M et al. demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. [Read the Full Post]

Lipopolysaccharide increases IL-6 secretion via activation of the ERK1/2 signaling pathway to up-regulate RANKL gene expression in MLO-Y4 cells

1244 | Aug 16 2017

Yu K et al. indicated that LPS up-regulates osteocyte expression of RANKL and IL-6, and the increased RANKL is associated with the up-regulation of IL-6, which involves the ERK1/2 pathway. [Read the Full Post]

BRG1 targeting STAT3/VEGFC signaling regulates lymphangiogenesis in colorectal cancer

1066 | Aug 09 2017

Zhu X et al. demonstration of the important roles of the BRG1/STAT3/VEGFC in tumor-associated lymphangiogenesis might lead to the discovery of novel therapeutic targets in the treatment of cancers with BRG1 loss of function. [Read the Full Post]

Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model

1694 | 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

1625 | 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]

17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib

3539 | Jul 26 2017

Girgert R et al. showed that reduction of GPER expression is a promising therapeutic approach for TNBC. [Read the Full Post]

Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

1944 | 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]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

2019 | 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

2450 | 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]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

2292 | 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

2071 | 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

4805 | 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

1499 | 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

2681 | 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]

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

1351 | 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 Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway

2312 | 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]

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

2104 | May 17 2017

Gage ZO et al. demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. [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

1773 | 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]

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]

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]

Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1

2090 | 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]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

2040 | Apr 18 2017

Yi H et al found weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [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

2093 | 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]

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

1521 | 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

2574 | 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]

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

1613 | 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

1832 | 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]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

2227 | 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]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells

2752 | 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

2785 | 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]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach

2301 | 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

2606 | 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]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

4947 | Sep 20 2016

Yi H et al. found that weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

Tcfap2c acts as a key factor in mammary tumorigenesis

4115 | 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

5245 | Mar 20 2015

Zhong et al. revealed that GPRC5A negatively regulates EGFR signaling and its downstream signaling STAT3. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

8253 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Molecular changes of the transformation of NSCLC to SCLC TKI-resistant EGFR mutant cancers

4082 | 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

5602 | 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]

Inactivating mutations of SMARCE1 promotes EGFR expression and suppress the responses to MET and ALK inhibitors in lung cancer

5705 | 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]

Tofacitinib promotes myeloid-derived suppressor cells expansion and reduces disease severity of arthritis SKG mice

5856 | 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]

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

10210 | Jan 07 2015

Winter et al. identified the underlying mechanism of the emerging JAK2 inhibitor therapy resistance in MPNs patients, and found the RAS and pathways mediated by AKT and ERK contribute to the resistance. [Read the Full Post]

An unusual mechanism of ERBB4 in regulating tumor related gene expression

8154 | 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]

The inhibition of JAK signaling promotes the conversion from white to brown adipocytes

7346 | 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]

The Notch signaling controls maintenance of memory CD4+ T cells

8552 | Dec 16 2014

Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. [Read the Full Post]

KIAA1199 provides a connection between oncogenic signaling of NF-κB and EGFR

5323 | 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

9260 | 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

8372 | 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

6049 | 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

7548 | 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

6965 | 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]

JAK2 and MPL are two main regulators of TPO-induced megakaryopoiesis

6177 | 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]

Neural stem cells "heal" target cells via extracellular vesicles

3585 | Oct 29 2014

Cossetti et al. found NPCs communicate to the host via extracellular vesicles (EVs) and also investigated the cytokine-regulated pathways involved in the communication. It comes to a novel view in the understanding the mechanisms of stem cell therapy. [Read the Full Post]

Endocrine therapy has become the most important systemic treatment

4239 | 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

3855 | Mar 07 2014

BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. [Read the Full Post]

WP1066 is a cell permeable AG 490 tyrphostin analog

5807 | 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]

Gefitinib is used to treat non small cell lung cancer in people

3918 | 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]

R428 inhibits angiogenesis in corneal micropocket and tumor models

4014 | 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]

This study is designed to evaluate the efficacy and safety of tofacitinib

6440 | 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]

Gefitinib were not considered clinically relevant

4685 | 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]

EGFR INHIBITORS AGAINST THE CANCERS

4326 | 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]

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]

EGFR INHIBITORS IN CANCER THERAPY

4567 | 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

4174 | 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]

ERLOTINIB– THE HCL SALT

4924 | 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]

GEFITINIB; AN EGFR INHIBITOR

4057 | 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]

GEFITINIB – EGFR REGULATING DRUG FOR LUNG CANCER

3798 | 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

3221 | 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]

GEFITINIB – EGFR REGULATOR IN LUNG CANCER

2997 | 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]

ERLOTINIB (OSI-420) – AN HCL SALT

3025 | 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]

GEFITINIB – REFGULATING EGFR in CANCER

2926 | Mar 19 2012

Introduction: The HER (EGFR) pathway and Gefitinib Protein kinases have been established in recent years as prime targets for selective inhibition in many disorders involving cell proliferation or cell migration. The extent of the protein kinase system is very large with hundreds of different proteins interacting together to send multitude of signals to nuclei determining growth, death, transcription or response to any form damage or stress. To enable understanding of the mechanism of action for all these proteins they have been classified under pathways which are directly related. One of these pathways that is significant in its effects is the HER pathway, originally known as the EGFR pathway in relation to the epithelial growth factor. However, more proteins related to EGFR were recognized (ErRB 2-4) and the HER family was born. The location of this series of proteins is too span across the cell membrane from the extracellular region (head) into the cytosole (tail). Attachment of ligands to the extracellular sites cause structural changes to the protein which expose tyrosine kinase binding domains in the section of the protein located in the cytosole. [Read the Full Post]

ERLOTINIB – A ONE STOP SHOP

2813 | Mar 19 2012

Introduction: The HER (EGFR) pathway and Erlotinib Extracellular and intercellular signaling is a major process in the regulation of the life and death of cells within in any tissue matrix. One of the most well known and significant of these signaling steams is the HER protein family pathway consisting of four distinct receptors. Originally this was solely recognized as HER1 receptor called, due to its ligand association and since it was primarily found in epithelial cells, the “epithelial growth factor receptor”. Abbreviated to the acronym EGFR this receptor has since been found to have a family of 3 other closely related protein receptors, HER 2-4. Unfortunately these were known as ErB2-4 before the relationship with EGFR was determined, since then the entire family has been renamed to the HER family. These receptors consist of an extracellular section (head) with a Trans-membrane section and a cytosolic section (tail). Ligands binding to the extracellular domains initiate a dimerization between receptors which in turn induce conformational changes. [Read the Full Post]

EGFR INHIBITORS VERSUS CANCER

2915 | Mar 20 2012

Introduction: The HER family of proteins Recently collated and renamed as a single family of homologous series of proteins the HER family represents a major group of cellular membrane signal transmitters. Confusingly in literature the new naming system is inconsistently followed and the four HER receptors are often referred to as EGFR (HER1; ErRB1), ErRB2 (HER2), ErRB3 (HER3) and ErRB4 (HER4). These receptors have a very specific mode of action in that extracellular ligands can bind to the surface receptor domains on the cell membrane. Binding to any one of four different versions the ligand can stimulate a number of possible responses. Upon binding, the complex formed will alter conformationally and dimerize with another HER receptor increasing the number of permutations possible in the signaling process. The Dimerization initiates changes in the conformational state of the protein that induces the intercellular segment of the protein to reveal binding domains previously hidden. The protein will auto-phosphorylate activating it to receiving intercellular protein binding which starts the signaling process with the cell. The number of pathways that can be activated in different ways is large leading to contradictory responses. [Read the Full Post]

CP-690550: THE CURE FOR ARTHRITIS

6130 | Mar 20 2012

Introduction: JAK and its role in signaling pathways The protein kinase family plays an essential role in the government of the growth or death properties of mammalian tissues. These proteins form an interrelated, redundant system that is capable of selectively initiating the growth of certain cell types in response to the needs of the host system. To do this the protein kinase super family is subdivided into a series of related protein kinases which make up a signaling pathway, traveling from the extracellular matrix into the cell nucleus. The Janus kinase pathway is one which is activated in response to the action of cytokines on the cytokine transmembrane receptors. Since these receptors have no kinase ability themselves they are total dependant on the Janus kinases (JAK) for activity. [Read the Full Post]

INCB18424 – JACKING THE JAK2

6809 | Mar 20 2012

Introduction: JAK2 in relation to metabolic blood disorders The transmission of signals from extracellular factors through the cell membrane to effect actions within the cell cytosole and nucleus is conducted along pathways of protein to protein interactions. Many metabolic disorders have been associated with aberrations in these pathways causing a variety of destructive cellular actions. Many of these diseases possess no known cure and in response research has focused on the mechanisms behind the progression of these diseases. One area that has received a lot of attention is the possibility that the natural immune function can be detrimental to healthy growth patterns if over stimulated by mutations in the genetic information of individuals. A key series of proteins in the immune response is the Janus kinases (JAK), a series of four distinct but domain related kinases located in the cellular cytosole. These kinases form a distinct link between extracellular immune function ligands and a direct regulation of transcription of genetic information. However, a mutation of the JAK2 isoform has been associated with degenerative effects such as myeloproliferative neoplasms, thrombocythemia, polycythemia vera and psoriasis. [Read the Full Post]

TASOCITINIB: THE REVOLUTION IN ARTHRITIS MANAGEMENT

6472 | Mar 18 2012

Introduction: Inhibition of the JAK pathway The protein kinases are a super family of protein that govern the control of cellular growth, creation of vascular structure and many other processes the control the way in which cells and tissue regenerate. In is estimated that 30% of all cellular regulation is governed by protein kinases. Protein kinases are subdivided into 7 different classifications of which one is the tyrosine kinases. These kinases operate by phosphorylation of a tyrosine amino acid residue transferring a signal down a cascade of protein to regulate cellular processes. A further subdivision of the tyrosine kinases can be made into receptor based kinases and non receptor based kinases. The Janus kinases (JAK) are a sub family of the receptor based tyrosine kinases. Signals from the JAK regulate the cytokines, the GM-CSF family and the GP130 receptor family. JAK kinases exist in the 4 distinct isoforms with twinned phosphorylation domains. Inhibitors of the JAK kinases have been demonstrated to have a positive effect on cancerous cells both in vivo and in vitro. [Read the Full Post]

RUXOLITINIB: THE JACK FOR JAK INHIBITION

6558 | Mar 13 2012

Ruxolitinib: Inhibition of the Janus Kinases The janus kinases are a sub family of the protein kinases and are refer to as non receptor tyrosine kinases. Signals from the Janus kinases regulate several different types of proteins such as the cytokine receptor family (interferon), the GM-CSF family and the GP130 receptor family. The JAK kinases occur in four isoforms, with two matching phosphorylation domains, one for activity one for regulation. JAK2 in been shown to be mutated in several conditions including thrombocthemia and myeloprliferation disorders. In relation to haematological maliganacies the JAK2 mutation have been shown to essential for tumor growth and proliferation. Inhibiting the JAK2 kinase offers a potential mechanism for chemotherapeutic action. Ruxolitinib is a small, molecule inhibitor that has been established to inhibit the Janus kinases; early clinic work established that Ruxolitinib has sufficient anti-tumor activity to warrant further investigation. [Read the Full Post]

EGFR INHIBITORS CONTROLLING TUMORIGENESIS

3578 | Mar 13 2012

Introduction: The EGFR’s role in the HER pathway A major pathway in the regulation of cell growth / death is the HER pathway, this pathway consists of four structurally related proteins primarily located in the cell membrane. The family members consist of HER1 (also known as EGFR), HER2 (also known as ErbB2), HER3 (also known as ErbB3) and HER4 (also known as ErbB4). These receptors consist of an extracellular head and an intracellular tail lying across the cell membrane. Ligands binding to the extracellular receptor induce conformational changes which reveal binding domains within the intracellular tail. Auto-phosphorylation of the tyrosine kinase domain is a result of the HER receptor forming dimers and depending on which of several different ligands induced the change the tail section attracts proteins to initiate signaling cascades to the nucleus. Ligands that trigger this signaling pathway consist of endothelial growth factor (EGF), transforming growth factor alpha (TGFα), beracellulin (BTC), epiregulin (EPR) and amphiregulin (AREG). [Read the Full Post]

Roles of PIM serine/threonine kinases in cancers

6534 | Oct 27 2011

The Pim family of Ser/Thr kinases has been first identified in murine Moloney leukemia virus induced lymphomas, and is composed of three isoforms, Pim-1, Pim-2 and Pim-3. The following studies show that Pims are constitutively activated in many cancers. Of which, Pim-1 and Pim-2 were found to show the elevated levels mostly in hematologic malignancies and prostate cancer, while increased Pim-3 expression was mainly observed in different solid tumors. [Read the Full Post]

Mumenthaler, S. M., P. Y. Ng, et al. (2009). "Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes." Mol Cancer Ther 8(10): 2882-2893.

4521 | Jul 17 2011

These findings support the idea that inhibiting Pim kinases, in combination with a chemotherapeutic agent, could play an important role in prostate cancer treatment by targeting the clinical problem of chemoresistance. [Read the Full Post]

Chen, L. S., S. Redkar, et al. (2009). "Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells." Blood 114(19): 4150-4157.

4234 | Jun 6 2011

Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction. [Read the Full Post]

Bianco, R., T. Gelardi, et al. (2007). "Rational bases for the development of EGFR inhibitors for cancer treatment." Int J Biochem Cell Biol 39(7-8): 1416-1431.

3202 | May 11 2011

This article reviews the EGFR role in carcinogenesis and tumor progression as rational bases for the development of specific therapeutic inhibitors. [Read the Full Post]

Bachmann, M. and T. Moroy (2005). "The serine/threonine kinase Pim-1." Int J Biochem Cell Biol 37(4): 726-730.

4384 | Apr 16 2011

Pim-1 is able to phosphorylate different targets, most of which are involved in cell cycle progression or apoptosis. Pim-1 expression can be induced by several external stimuli in particular by a number of cytokines relevant in the immune system, which led to the labeling of Pim-1 as a "booster" for the immune response. [Read the Full Post]

Fischer, O. M., S. Hart, et al. (2003). "EGFR signal transactivation in cancer cells." Biochem Soc Trans 31(Pt 6): 1203-1208.

3117 | Mar 11 2011

Together with investigations revealing the importance of this GPCR-EGFR cross-talk mechanism in cardiac hypertrophy, Helicobacter pylori -induced pathophysiological processes and cystic fibrosis, these findings support an important role for GPCR ligand-dependent EGFR signal transactivation in diverse pathophysiological disorders. [Read the Full Post]