Has MET met its match?

The last decade has seen a revolution in both our understanding of the genomic landscape of a wide range of malignancies and the recognition that a spectrum of tumors harbors dominant oncogenic alterations leading to a unique dependence of these tumors to the presence/activity of the oncogene, called oncogene addiction. In tumors where the activity of such oncogenic gene products can be successfully inhibited pharmacologically, responses can be dramatic. Leading examples of such aberrations include BCR-ABL positive chronic myeloid leukemia, KIT-mutated gastrointestinal stromal tumor (GIST) sarcomas and epidermal growth factor receptor (EGFR)-mutated lung adenocarcinomas, and in patients with these tumors, the treatment landscape has been completely redrawn. With the advent of high-throughput genomics technology and through major international collaborative efforts, such as The Cancer Genome Atlas (TCGA), comprehensive information is now available of genomic alterations in many common and less common malignancies leading some to question whether the information to be learned about highly actionable alterations is reaching saturation. It is with this background that we will review recent major findings, including the manuscript of Frampton et al. (1), leading to a breakthrough in our understanding of the oncogenic role and long-proposed but elusive actionability of the MET tyrosine kinase.