Skipping the line: bringing MET exon 14 skipping mutations to the forefront of targeted therapy

Our understanding of the oncogenic role and targetability of the mesenchymal-to-epithelial transition ( MET ) oncogene in non-small cell lung cancer (NSCLC) has made remarkable strides in the last year through the discovery of recurrent, actionable MET exon 14 skipping alterations in NSCLC. The MET gene, located at chromosome 7, encodes for the hepatocyte growth factor (HGF) receptor, a tyrosine kinase receptor important for cell proliferation, apoptosis and motility/invasion and has long been believed to be a potentially relevant oncogene in certain settings. In fact, recurrent MET gene mutations had been reported in certain types of papillary renal cell cancer, including familial cases, and sporadic MET mutations have been previously reported in NSCLC, however until recently, targeting MET in NSCLC has been fraught with challenges (1). Several groups have now reported their observations of recurrent, actionable MET exon 14 alterations, generating greater interest and improved clarity in the potential incorporation of MET testing and MET targeting into current treatment algorithms in this age of personalized medicine. We will hereby review the recent important study of Awad and colleagues in the context of other recent discoveries dramatically changing the diagnostic and treatment landscape in this field.