Amplification of Wild-type KRAS Imparts Resistance to Crizotinib in MET Exon 14 Mutant Non-Small Cell Lung Cancer.
Magda BahcallMark M AwadLynette M ShollFrederick H WilsonMan XuStephen WangSangeetha PalakurthiJihyun ChoiElena V IvanovaGiulia C LeonardiBryan C UlrichCloud P PaweletzPaul T KirschmeierMasayuki WatanabeHideo BabaMizuki NishinoRebecca J NagyRichard B LanmanMarzia CapellettiEmily S ChambersAmanda J RedigPaul A VanderLaanDaniel B CostaYu ImamuraPasi A JännePublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2018)
Using patient-derived cell line and xenografts, we characterize the mechanism of crizotinib resistance mediated by KRAS amplification in METex14-mutant NSCLC and demonstrate the superior efficacy of the dual MET/PI3K inhibition as a therapeutic strategy addressing this resistance mechanism.