Blog of Signaling Pathways

[Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib]

56 views | Jun 22 2023

Savolitinib, a specific tyrosine kinase inhibitor targeting the MET protein, has been approved in China for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations, and studies are ongoing to evaluate its efficacy in patients with other MET abnormalities. [Read the Full Post]

TK216 targets microtubules in Ewing sarcoma cells

86 views | Jun 22 2023

The study reveals that TK216, initially developed as an EWSR1-FLI1 inhibitor, acts as a microtubule destabilizing agent, explaining its cytotoxicity and supporting a reevaluation of its clinical trials in combination with vincristine. [Read the Full Post]

JAK/BCL2 inhibition acts synergistically with LSD1 inhibitors to selectively target ETP-ALL

0 views | Jun 22 2023

The combination of a LSD1 inhibitor with a JAK/STAT pathway inhibitor or a BCL2 inhibitor reverses resistance and efficiently inhibits the growth of ETP-ALL cells, suggesting a potential novel combination therapy for ETP-ALL patients. [Read the Full Post]

A Novel Tri-Functional Liposome Re-Educates "Cold Tumor" and Abrogates Tumor Growth by Synergizing Autophagy Inhibition and PD-L1 Blockade

50 views | Jun 22 2023

This study demonstrates that a tri-functional liposomal system, DOX-SAR-JY4LIPO, combining doxorubicin, a VPS34 inhibitor, and an anti-PD-L1 peptide, effectively converts "cold tumors" into "hot tumors" by increasing immune cell infiltration and shows promise for improving cancer immunotherapy. [Read the Full Post]

The role of small GTPases in bisphenol AF-induced multinucleation in comparison with dibutyl phthalate in the male germ cells

111 views | Jun 22 2023

This study demonstrates that BPAF exposure leads to cytotoxicity, increased multinucleation in mouse spermatogonia cells, and highlights the involvement of small GTPase-signaling pathways in mediating these effects, providing insights into the genotoxic mechanisms of BPA analogs on male germ cells. [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

119 views | 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]

Characterization of cell line with dedifferentiated GIST-like features established from cecal GIST of familial GIST model mice

58 views | Jun 21 2023

The study established a cell line derived from cecal GIST in a familial GIST mouse model, characterized as dedifferentiated GIST-like cells with high expression of HSP90 families and glutaminase 1, and identified the combination of Pimitespib and Telaglenastat as a potential treatment strategy for these cells. [Read the Full Post]

Suppression of lung oxidative stress, inflammation and fibrosis following nitrogen mustard exposure by the selective farnesoid X receptor agonist obeticholic acid

49 views | Jun 21 2023

Activation of the farnesoid X receptor (FXR) through treatment with obeticholic acid attenuates nitrogen mustard-induced lung injury, oxidative stress, inflammation, and fibrosis, suggesting FXR activation as a potential therapeutic strategy for limiting cytotoxic vesicant toxicity. [Read the Full Post]

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

93 views | 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]

Effect of insulin-like growth factor system on luteinising angiogenesis

78 views | Jun 21 2023

This study found that while exogenous IGF1 and IGF2 had limited effects on luteinizing follicular angiogenesis and progesterone production, inhibiting the IGF1 receptor signaling significantly reduced endothelial cell growth and progesterone concentration, indicating its crucial role in these processes. [Read the Full Post]

Three dimensional models of dedifferentiated liposarcoma cell lines: scaffold-based and scaffold-free approaches

135 views | Jun 20 2023

This study aimed to establish 3D cell culture models of liposarcomas using different methods, observing distinct structural differences and demonstrating the potential of these models to provide new insights into efficacy and toxicity, serving as an important step in the pre-clinical phase prior to clinical trials. [Read the Full Post]

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

109 views | 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 views | 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]

Targeting CXCL1 chemokine signaling for treating cisplatin ototoxicity

66 views | Jun 20 2023

This study demonstrates that inhibiting the CXCL1-CXCR2 pathway through trans-tympanic administration of SB225002 or CXCR2 siRNA protects against cisplatin-induced hearing loss, preserves hair cell integrity, and reduces the expression of inflammatory mediators associated with ototoxicity. [Read the Full Post]

Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response

53 views | 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

112 views | 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]

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance

85 views | Jun 19 2023

The 2023 statement on homozygous familial hypercholesterolaemia (HoFH) provides updated clinical guidance, emphasizing phenotypic features over genotype, prioritizing combination LDL-C-lowering therapy, and recommending the creation of national screening programs and education initiatives to address global inequities in HoFH care. [Read the Full Post]

NAT10 Drives Cisplatin Chemoresistance by Enhancing ac4C-Associated DNA Repair in Bladder Cancer

24 views | Jun 19 2023

The study reveals that the RNA modification ac4C, mediated by NAT10, promotes cisplatin chemoresistance in bladder cancer by enhancing DNA damage repair through stabilization of AHNAK mRNA, and targeting NAT10 could be a potential therapeutic approach to overcome cisplatin resistance in bladder cancer. [Read the Full Post]

Therapeutic potential of CDK11 in cancer

123 views | Jun 19 2023

The discovery that CDK11 regulates pre-mRNA splicing and the identification of OTS964 as a CDK11 inhibitor with antiproliferative properties highlight the therapeutic potential of targeting CDK11 in cancer treatment. [Read the Full Post]

MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1

69 views | Jun 19 2023

MI-773, a specific antagonist of MDM2, disrupts the MDM2/p53 axis, leading to suppressed proliferation, induced apoptosis, and cell cycle arrest in neuroblastoma cells, suggesting its potential as a novel treatment strategy for this pediatric malignancy. [Read the Full Post]