Blog of Signaling Pathways

The expression and role of glycolysis-associated molecules in infantile hemangioma

86 views | Aug 13 2023

This study demonstrates that glycolysis-associated molecules are highly expressed in infantile hemangioma endothelial cells, and their inhibition leads to a reduction in cell proliferation, migration, and tube formation, suggesting their potential as therapeutic targets for treating infantile hemangioma. [Read the Full Post]

Safety and efficacy of single insertion accelerated MR-image guided brachytherapy following chemo-radiation in locally advanced cervix cancer: modifying our EMBRACE during the COVID pandemic

28 views | Aug 13 2023

The study showed that a modified image-guided adaptive brachytherapy protocol (mIGABT) was effective, cost-saving, and well-tolerated in treating locally advanced cervical cancer during the COVID-19 pandemic. [Read the Full Post]

BRCAness, Homologous Recombination Deficiencies, and Synthetic Lethality

29 views | Aug 13 2023

BRCAness refers to a tumor's homologous recombination repair defect, either through genetic inactivation of BRCA or HRD genes, and can be identified through genomic profiling, with implications for selecting targeted therapies such as PARP inhibitors, TOP1 inhibitors, and platinum derivatives. [Read the Full Post]

Advanced ovarian clear cell carcinoma with RAD50 mutation treated by PARP inhibitor pamiparib combined with anti-angiogenesis therapy: a case report

35 views | Aug 13 2023

Targeted combination therapy with the PARP inhibitor pamiparib and bevacizumab showed promising results in achieving partial remission and improving the quality of life in a 45-year-old female patient with advanced ovarian clear cell carcinoma (OCCC) and a RAD50 mutation. [Read the Full Post]

Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy

22 views | Aug 12 2023

The study demonstrates that combining MAPK inhibitors, FASN inhibitors, and ROS-inducing compounds increases lipid poly-unsaturation and overcomes therapy resistance, leading to improved survival in BRAF-mutant melanoma. [Read the Full Post]

HDAC inhibitor chidamide overcomes drug resistance in chronic myeloid leukemia with the T315i mutation through the Akt-autophagy pathway

114 views | Aug 12 2023

Chidamide, a Histone Deacetylase Inhibitor (HDACi) drug, shows promising anti-leukemia effects and has the potential to overcome T315I mutation-related drug resistance in Chronic Myeloid Leukemia (CML) when used in combination with Tyrosine Kinase Inhibitors (TKIs). [Read the Full Post]

Second-line Endocrine Therapy of Hormone Receptor-Positive/HER2-negative Advanced Breast Cancer: A Systematic Review and Network Meta-analysis

59 views | Aug 12 2023

The network meta-analysis found that cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with fulvestrant (Ful500) demonstrated the best progression-free survival (PFS) and overall survival (OS) outcomes as second-line therapy for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced/metastatic breast cancer, with palbociclib ranking first in terms of PFS and CDK4/6i ranking first in terms of OS. [Read the Full Post]

Targeting DNA Repair with Combined Inhibition of NHEJ and MMEJ Induces Synthetic Lethality in TP53-Mutant Cancers

40 views | Aug 12 2023

Combining the DNA-PK/NHEJ inhibitor peposertib with the POLθ/MMEJ inhibitor novobiocin provides a rational treatment strategy for TP53-mutant solid tumors, resulting in synthetic lethality and potential therapeutic efficacy. [Read the Full Post]

Synergistic Targeting of DNA-PK and KIT Signaling Pathways in KIT Mutant Acute Myeloid Leukemia

33 views | Aug 12 2023

This study demonstrates that targeting DNA-PK in KIT mutant acute myeloid leukemia (AML) cells, in combination with inhibitors of KIT signaling, shows synergistic effects and holds promise as a therapeutic strategy for this aggressive form of AML. [Read the Full Post]

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

0 views | Aug 11 2023

This study demonstrates that pexidartinib, a CSF-1R inhibitor, alone or in combination with a PD-1 inhibitor, shows significant tumor shrinkage and enhanced antitumor immune responses in a rat model of esophageal adenocarcinoma, providing a promising combinatorial strategy for future clinical approaches. [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 views | 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]

Activation of skeletal muscle FAPs by LPA requires the Hippo signaling via the FAK pathway

60 views | Aug 11 2023

Lysophosphatidic acid (LPA) activates fibro/adipogenic progenitors (FAPs) in skeletal muscle by signaling through LPA1, promoting FAK phosphorylation and subsequent activation of the Hippo pathway. [Read the Full Post]

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

46 views | 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

81 views | 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]

Caveolae-associated protein 3 promotes adipogenic differentiation of porcine preadipocytes by promoting extracellular signal-regulated kinase phosphorylation

31 views | Aug 10 2023

The study demonstrated that CAVIN3 promotes adipogenic differentiation of porcine preadipocytes by enhancing ERK phosphorylation, providing insights into the molecular mechanism of porcine fat deposition. [Read the Full Post]

Fueling the Pipeline via Innovations in Organic Synthesis

16 views | Aug 10 2023

Synthetic organic chemistry, particularly through the involvement of Discovery Synthesis Groups like AbbVie's Centralized Organic Synthesis (COS), is of paramount importance in the pharmaceutical industry as it accelerates the drug discovery process, addresses synthetic accessibility challenges, and contributes to the development of advanced drug candidates in various therapeutic areas. [Read the Full Post]

Novel Correctors and Potentiators Enhance Translational Readthrough in CFTR Nonsense Mutations

33 views | Aug 10 2023

The study evaluated the effectiveness of novel CFTR correctors, potentiators, and readthrough compounds in restoring CFTR function in cells with premature-termination codon (PTC) mutations, showing promising results for the potential treatment of cystic fibrosis. [Read the Full Post]

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

16 views | 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 views | 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]

The Novel Lysosomal Autophagy Inhibitor (ROC-325) Ameliorates Experimental Pulmonary Hypertension

63 views | Aug 09 2023

ROC-325, a small molecule autophagy inhibitor, demonstrates therapeutic potential for pulmonary hypertension by inhibiting autophagy, reducing HIF levels, and increasing nitric oxide production. [Read the Full Post]