Oncogenic MET as an Effective Therapeutic Target in Non-Small Cell Lung Cancer Resistant to EGFR Inhibitors: The Rise of the Phoenix

Abstract

Anecdotal reports have shown that concomitant inhibition of EGFR and MET can be clinically effective in patients with non-small cell lung cancer carrying EGFR mutations and MET amplification, but large phase III trials in genetically unselected individuals have failed to confirm the benefit of this combination therapy. A new study corroborates the evidence that lung cancer susceptibility to EGFR and MET blockade is sustained by genetically based activation of both targets and identifies a mutation in MET that confers acquired resistance to standard MET inhibitors hitting the active kinase, yet is vulnerable to other MET-directed compounds with a different binding mode. Cancer Discov; 6(12); 1306-8. ©2016 AACR.See related article by Bahcall and colleagues, p. 1334.