Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring met mutations causing exon 14 skipping Journal Article
| Authors: | Paik, P. K.; Drilon, A.; Fan, P. D.; Yu, H.; Rekhtman, N.; Ginsberg, M. S.; Borsu, L.; Schultz, N.; Berger, M. F.; Rudin, C. M.; Ladanyi, M. |
| Article Title: | Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring met mutations causing exon 14 skipping |
| 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. ©2015 American Association for Cancer Research. |
| Keywords: | adult; clinical article; controlled study; human tissue; treatment response; aged; middle aged; gene mutation; gene deletion; fatigue; drug dose reduction; positron emission tomography; prospective study; computer assisted tomography; phase 2 clinical trial; gene amplification; gene expression; genetic variability; cancer inhibition; lung adenocarcinoma; fluorodeoxyglucose; scatter factor receptor; crizotinib; next generation sequencing; cabozantinib; very elderly; human; male; female; article; exon skipping |
| Journal Title: | Cancer Discovery |
| Volume: | 5 |
| Issue: | 8 |
| ISSN: | 2159-8274 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2015-08-01 |
| Start Page: | 842 |
| End Page: | 849 |
| Language: | English |
| DOI: | 10.1158/2159-8290.cd-14-1467 |
| PROVIDER: | scopus |
| PUBMED: | 25971939 |
| PMCID: | PMC4658654 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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