MET exon 14 deletion (METex14): finally, a frequent-enough actionable oncogenic driver mutation in non-small cell lung cancer to lead MET inhibitors out of “40 years of wilderness” and into a clear path of regulatory approval

The hepatocyte growth factor (HGF) ligand and its receptor MET (mesenchymal-epithelial transition) tyrosine kinase receptor axis has long been demonstrated to be important in oncogenesis and metastasis in multiple tumor types. Mechanisms of dysregulation of the HGF-MET axis includes over-expression of the HGF ligand, activating point mutations in MET, MET gene amplification, MET protein over-expression and potentially MET rearrangements. Many structural different MET tyrosine kinase inhibitors (TKIs) have been developed to target the HGF-MET axis pathway but so far the results have been disappointing (1).