Preexistence and Clonal Selection of MET Amplification in EGFR Mutant NSCLC

摘要: MET amplification activates ERBB3/PI3K/AKT signaling in EGFR mutant lung cancers and causes resistance to kinase inhibitors. We demonstrate that activation by its ligand, HGF, also induces drug resistance, but through GAB1 signaling. Using high-throughput FISH analyses both cell lines patients with cancer, we identify subpopulations of cells prior exposure. Surprisingly, HGF accelerates the development vitro vivo. inhibitor due either or autocrine production, was cured vivo combined inhibition. These findings highlight potential prospectively treatment naive, EGFR-mutant cancer who will benefit from initial combination therapy.