Document Detail

Biological significance and targeting of c-Met tyrosine kinase receptor in cancer.
MedLine Citation:
PMID:  23276936     Owner:  NLM     Status:  MEDLINE    
c-Met is a tyrosine kinase receptor largely described to be involved in cancer progression and metastasis. In such pathologic situation, many alterations of this receptor were noticed that include transcriptional overexpression, gene amplification, somatic or germline mutations and/or ligand dependent autocrine/paracrine loops. More recently it has also been suggested that c-Met would be involved in resistance to targeted therapies directed towards EGFR or angiogenesis. Major efforts from a large number of pharmaceutical companies are invested dedicated to evaluate the efficacy of either small molecule inhibitors or monoclonal antibodies directed against c-Met or its unique ligand HGF. A series of promising results from the first completed clinical trials indicated that compounds targeting c-Met have an acceptable toxicity profile and that efficacy was noticed in some treated patients. Non squamous NSCLC patients that express more often high levels of c-Met seemed to represent a most sensitive subset for and anti-c-Met/erlotinib therapy. Many Phase III trials are currently recruiting and a particular effort was performed in order to discover biomarkers associated with efficacy and patient selection. This review will provide an overview of the current knowledge on the c-Met axis for development of novel therapeutics in Oncology.
Liliane Goetsch; Veronique Caussanel; Nathalie Corvaia
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Publication Detail:
Type:  Journal Article; Review     Date:  2013-01-01
Journal Detail:
Title:  Frontiers in bioscience (Landmark edition)     Volume:  18     ISSN:  1093-4715     ISO Abbreviation:  Front Biosci (Landmark Ed)     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-06-12     Revised Date:  2013-07-29    
Medline Journal Info:
Nlm Unique ID:  101612996     Medline TA:  Front Biosci (Landmark Ed)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  454-73     Citation Subset:  IM    
Centre d'Immunologie Pierre Fabre, 5 avenue Napoleon III, F-74164 Saint Julien en Genevois, France.
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MeSH Terms
Antibodies, Monoclonal / therapeutic use
Clinical Trials as Topic
Hepatocyte Growth Factor / metabolism
Neoplasms / drug therapy,  physiopathology*
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins c-met / biosynthesis,  genetics,  immunology,  physiology*
Pyrrolidinones / therapeutic use
Quinolines / therapeutic use
Receptor, Epidermal Growth Factor / physiology
Receptor, erbB-2 / physiology
Signal Transduction
Reg. No./Substance:
0/ARQ 197; 0/Antibodies, Monoclonal; 0/Protein Kinase Inhibitors; 0/Pyrrolidinones; 0/Quinolines; 67256-21-7/Hepatocyte Growth Factor; EC protein, human; EC Proteins c-met; EC, Epidermal Growth Factor; EC, erbB-2

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