Antitumor Activity of DFX117 by Dual Inhibition of c-Met and PI3Kα in Non-Small Cell Lung Cancer

摘要: Aberrant activation of hepatocyte growth factor (HGF)/c-Met signaling pathway caused by gene amplification or mutation plays an important role in tumorigenesis. Therefore, c-Met is considered as attractive target for cancer therapy and inhibitors have been developed with great interests. However, cancers treated inevitably develop resistance commonly the PI3K/Akt signal transduction pathway. combination PI3Kα showed synergistic activities, especially, hyperactivated PIK3CA-mutated cells. In our previous study, we rationally designed synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) a novel selective inhibitor. Herein, antitumor activity underlying mechanisms DFX117 against non-small cell lung (NSCLC) cells were evaluated both vitro vivo animal models. Concurrent targeted dose-dependent inhibited H1975 (PIK3CA amplification) A549 (KRAS mutation). subsequently induced G0/G1 cycle arrest apoptosis. These data highlight significant potential feasible efficacious agent treatment NSCLC patients.