ArticleBritish journal of cancer2024
Epithelial-mesenchymal transition status is a remarkable biomarker for the combination treatment with avutometinib and defactinib in KRAS-mutated non-small cell lung cancer.
Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Focal adhesion kinase inhibitor defactinib enhances olaparib-induced suppression of BRCA-proficient breast cancer cell proliferation.Oncology letters · 2026Article
- Combined FAK and MEK inhibition suppresses chromosome 8 gain malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Avutometinib and Defactinib: First Approval.Drugs · 2025Review
- Targeting Focal Adhesion Kinase in Lung Diseases: Current Progress and Future Directions.Biomolecules · 2025Review
- Anti-tumor efficacy of RAF/MEK inhibitor VS6766 in KRAS-mutated colorectal cancer cells.Cancer chemotherapy and pharmacology · 2025Article
- Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases.Cell reports. Medicine · 2025Article
- Pan-Immune-Inflammation Value (PIV) and Prognostic Nutritional Index (PNI) are Associated with Distant Metastasis in Colorectal Cancer withInternational journal of general medicine · 2025Article
- The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma.Cancer research communications · 2024Article
- Preclinical evaluation of avutometinib and defactinib in high-grade endometrioid endometrial cancer.Cancer medicine · 2024Article
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Abstract
backgroundRecent therapeutic strategies for KRAS-mutated cancers that inhibit the MAPK pathway have attracted considerable attention. The RAF/MEK clamp avutometinib (VS-6766/CH5126766/RO5126766/CKI27) is promising for patients with KRAS-mutated cancers. Although avutometinib monotherapy has shown clinical activity in patients with KRAS-mutated cancers, effective combination strategies will be important to develop.
methodsUsing a phosphorylation kinase array kit, we explored the feedback mechanism of avutometinib in KRAS-mutated NSCLC cells, and investigated the efficacy of combining avutometinib with inhibitors of the feedback signal using in vitro and in vivo experiments. Moreover, we searched for a biomarker for the efficacy of combination therapy through an in vitro study and analysis using the The Cancer Genome Atlas Programme dataset.
resultsFocal adhesion kinase (FAK) phosphorylation/activation was increased after avutometinib treatment and synergy between avutometinib and FAK inhibitor, defactinib, was observed in KRAS-mutated NSCLC cells with an epithelial rather than mesenchymal phenotype. Combination therapy with avutometinib and defactinib induced apoptosis with upregulation of Bim in cancer cells with an epithelial phenotype in an in vitro and in vivo study.
conclusionsThese results demonstrate that the epithelial-mesenchymal transition status may be a promising biomarker for the efficacy of combination therapy with avutometinib and defactinib in KRAS-mutated NSCLC.
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