Research Paper Volume 13, Issue 5 pp 6890—6903

MET inhibitor, capmatinib overcomes osimertinib resistance via suppression of MET/Akt/snail signaling in non-small cell lung cancer and decreased generation of cancer-associated fibroblasts

Cancer associated fibroblasts (CAFs) from osimertinib-resistant patients promoted osimertinib resistance via HGF/MET signaling and induction of epithelial-to-mesenchymal transition (EMT) and transformed NSCLC cells into TKI resistant stem-like cells. The treatment of capmatinib (MET inhibitor) inhibited CAF-mediated MET/Akt activation bypassing EGFR signaling pathway and re-sensitizing NSCLC towards osimertinib.

Figure 6. Cancer associated fibroblasts (CAFs) from osimertinib-resistant patients promoted osimertinib resistance via HGF/MET signaling and induction of epithelial-to-mesenchymal transition (EMT) and transformed NSCLC cells into TKI resistant stem-like cells. The treatment of capmatinib (MET inhibitor) inhibited CAF-mediated MET/Akt activation bypassing EGFR signaling pathway and re-sensitizing NSCLC towards osimertinib.