Issues

Paik and colleagues identified MET splice site mutations that result in exon 14 skipping in 4% of patients with stage IV lung adenocarcinoma and observed clinical responses to crizotinib or cabozantinib, small-molecule tyrosine kinase inhibitors with activity against MET, in 4 patients with MET exon 14 splice site mutations. In a related study, Frampton and colleagues identified diverse MET exon 14 alterations across several cancer types in addition to lung adenocarcinomas, provided preclinical evidence that these mutations are oncogenic and confer sensitivity to MET inhibition, and reported clinical responses to crizotinib or the MET-selective inhibitor capmatinib in 3 patients with MET exon 14 alterations. Together, these findings suggest that MET exon 14 splice site mutations are actionable and that patients with these mutations may benefit from MET-targeted therapies. For details, please see the article by Paik and colleagues on page 842 and the article by Frampton and colleagues on page 850.