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Targeting c-MET in the battle against advanced nonsmall-cell lung cancer.
MedLine Citation:
PMID:  23385860     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: The mesenchymal-epidermal transition (c-MET) receptor tyrosine kinase has a central role in the cancer cell's survival. MET and its ligand, hepatocyte growth factor (HGF), have recently been identified as promising targets in solid tumors, including nonsmall-cell lung cancer (NSCLC).
RECENT FINDINGS: Aberrant MET activation can be the result of different mechanisms such as MET and HGF overexpression, MET gene amplification or mutation. Retrospective studies in NSCLC showed that MET gene copy number is a negative prognostic factor, although few data are available on the role of MET mutations. In preclinical models, cell lines with MET gene amplification are extremely sensitive to MET inhibition. Although the inner presence of gene amplification is a rare event (1-7% cases), MET amplification has emerged as one of the critical events for acquired resistance in epidermal growth factor receptor (EGFR) mutated lung adenocarcinomas refractory to EGFR-tyrosine kinase inhibitors (TKIs). In NSCLC with acquired resistance to EGFR-TKIs, MET amplification occurs in up to 20% cases and preclinical and clinical data indicated MET and EGFR co-inhibition as a potential effective strategy to overcome resistance.
SUMMARY: MET has recently emerged as a promising target, and ongoing trials will clarify the role of anti-MET strategies in NSCLC.
Authors:
Lorenza Landi; Gabriele Minuti; Armida D'Incecco; Federico Cappuzzo
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current opinion in oncology     Volume:  25     ISSN:  1531-703X     ISO Abbreviation:  Curr Opin Oncol     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007265     Medline TA:  Curr Opin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  130-6     Citation Subset:  IM    
Affiliation:
Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
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