Tong Dai
MET is a tyrosine kinase receptor involved in cell proliferation, survival, and migration. MET pathway is activated in cancer by gene amplification and overexpression, ligand overexpression and autocrine/paracrine activation, and activating MET mutations. MET dysregulation is also found to be responsible for resistance to treatment and targeted therapy including EGFR TKIs for NSCLC. Preclinical studies and early phase clinical trials of inhibitors of HGF-MET pathway showed encouraging results but several late phase clinical trials failed. In trials evaluating drugs designed to inhibit HGF-MET binding, patient selection may explain the lack of efficacy in those carrying MET amplification or activating mutations. Novel drugs capable of inducing MET degradation in addition to targeting HGF-MET binding have great potential in blocking MET oncogenic pathway and demonstrating clinical efficacy.
