Targeting the c-MET signaling pathway for cancer therapy.
BACKGROUND
In many human cancers, c-MET is activated via receptor overexpression, amplification, mutation and/or a ligand-dependent autocrine/paracrine loop. These biochemical and genetic abnormalities have been correlated with poor clinical outcomes and drug resistance in cancer patients. Preclinical studies suggest that targeting aberrant c-MET signaling could be an attractive therapy in cancer, but this notion has only recently been tested in the clinic.


OBJECTIVE
To describe the biological aspects of the c-MET signaling pathway and to discuss recent progress and possible future trends in the development of agents that target the c-MET pathway, with an emphasis on small-molecule c-MET kinase inhibitors.


METHODS
A review of relevant publications, including published articles in literature, reports at scientific meetings, and information available through the Internet.


CONCLUSIONS
The dysregulated c-MET pathway represents a promising target for cancer drug development. The agents that target the c-MET pathway have demonstrated impressive evidence of early clinical activity and may have a significant therapeutic potential.
Liu
Xiangdong
X
Incyte Corporation, Experimental Station, Rt. 141 & Henry Clay Road, Wilmington, DE 19880, USA. xliu@incyte.com
Yao
Wenqing
W
Newton
Robert C
RC
Scherle
Peggy A
PA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met