4.5 Review

Targeting the c-MET signaling pathway for cancer therapy

Journal

EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 17, Issue 7, Pages 997-1011

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1517/13543784.17.7.997

Keywords

cancer; c-MET; hepatocyte growth factor; receptor tyrosine kinase; signal transduction; small-molecule kinase inhibitor

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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. Objectives: 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. Method: A review of relevant publications, including published articles in literature, reports at scientific meetings, and information available through the Internet. Results/conclusion: 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.

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