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Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping.
- Source :
-
Cancer discovery [Cancer Discov] 2015 Aug; Vol. 5 (8), pp. 842-9. Date of Electronic Publication: 2015 May 13. - Publication Year :
- 2015
-
Abstract
- Unlabelled: 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-ubiquitin 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.<br />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.<br /> (©2015 American Association for Cancer Research.)
- Subjects :
- Adenocarcinoma diagnosis
Adenocarcinoma mortality
Adenocarcinoma of Lung
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols therapeutic use
DNA Copy Number Variations
Female
Humans
Lung Neoplasms diagnosis
Lung Neoplasms mortality
Male
Middle Aged
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Positron-Emission Tomography
Proto-Oncogene Proteins c-met antagonists & inhibitors
Proto-Oncogene Proteins c-met metabolism
RNA Splice Sites
Treatment Outcome
Adenocarcinoma drug therapy
Adenocarcinoma genetics
Alternative Splicing
Antineoplastic Agents therapeutic use
Exons
Lung Neoplasms drug therapy
Lung Neoplasms genetics
Mutation
Protein Kinase Inhibitors therapeutic use
Proto-Oncogene Proteins c-met genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2159-8290
- Volume :
- 5
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer discovery
- Publication Type :
- Academic Journal
- Accession number :
- 25971939
- Full Text :
- https://doi.org/10.1158/2159-8290.CD-14-1467