Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring met mutations causing exon 14 skipping

Paul K. Paik, Alexander Drilon, Pang Dian Fan, Helena Yu, Natasha Rekhtman, Michelle S. Ginsberg, Laetitia Borsu, Nikolaus Schultz, Michael F. Berger, Charles M. Rudin, Marc Ladanyi

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in the MET exon 14 RNA splice acceptor and donor sites, which lead to exon skipping, deletion of the juxtamembrane domain containing the CBL E3-ubiq-uitin ligase-binding site, and decreased turnover of the resultant aberrant MET protein, were previously reported to be oncogenic in preclinical models. We now report responses to the MET inhibitors crizotinib and cabozantinib in four patients with stage IV lung adenocarcinomas harboring mutations leading to MET exon 14 skipping, highlighting a new therapeutic strategy for the 4% of lung adenocarcinoma patients whose tumors harbor this previously underappreciated genetic alteration. Significance: Oncogenic mutations in the MET exon 14 splice sites that cause exon 14 skipping occur in 4% of lung adenocarcinomas. We report responses to the MET inhibitors crizotinib and cabozantinib in patients with lung adenocarcinomas harboring MET exon 14 splice site mutations, identifying a new potential therapeutic target in this disease.

Original languageEnglish (US)
Pages (from-to)842-850
Number of pages9
JournalCancer Discovery
Volume5
Issue number8
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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