The expanding role of the receptor tyrosine kinase MET as a therapeutic target in non-small cell lung cancer.

Abstract

Aberrant regulation of MET receptor tyrosine kinase activity is a frequent event in non-small cell lung cancer (NSCLC), even though the frequency of oncogenic driver mutations of MET is low. Our discovery of oncogenic MET exon 14 skipping mutations, the characterization of the first prototype MET kinase inhibitor, and characterization of MET expression levels have led the way to novel therapeutic approaches with improved outcomes in NSCLC. MET exon 14 mutations are the most consequential but not the only alterations that can be targeted through small molecule tyrosine kinase inhibitors. The abundant expression of cellular MET (c-MET) in cancer cells has provided new opportunities for immuno-oncology approaches in a broader patient population, and the integration of MET-targeted personalized medicine with immunotherapy has not been fully exploited yet. Here, we highlight essential facets of MET as a therapeutic target in NSCLC and provide an outlook for future approaches.