HGF/c-MET Targeted Therapeutics: Novel Strategies for Cancer Medicine

Author(s): Timothy A. Yap , Shahneen K. Sandhu , Salma M. Alam , Johann S. de Bono .

Journal Name: Current Drug Targets

Volume 12 , Issue 14 , 2011

Become EABM
Become Reviewer

Abstract:

The hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/c-MET) receptor tyrosine kinase (RTK) pathway plays a pleotropic role in cell proliferation, migration, invasion, angiogenesis and survival. Although it has critical physiological functions in embryonic development and tissue repair, this signaling cascade is frequently deregulated in a wide range of tumors. Aberrant HGF/c-MET signaling, driven by various mechanisms, including constitutive activation and over-expression, has multifunctional effects in oncogenesis and is implicated in the acquisition of an aggressive phenotype with metastatic potential. The central role of c-MET activity in cancer progression, as well as disparities between quiescent HGF/c-MET signaling in normal tissue and overexpression in tumor may provide a degree of tumor selectivity for therapeutic intervention, making HGF or c-MET inhibition an attractive proposition in oncology. This review focuses on the underlying oncogenic role of aberrant HGF/c-MET signaling in malignant progression, as well as recent preclinical and clinical data on the different strategies employed in inhibiting HGF/c-MET function.

Keywords: Hepatocyte growth factor, c-MET, targeted therapeutics, personalizd medicine, ARQ 197, MetMAb, monoclonal antibodies, small molecule inhibitors, clinical trials, cancer

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 12
ISSUE: 14
Year: 2011
Page: [2045 - 2058]
Pages: 14
DOI: 10.2174/138945011798829348
Price: $58

Article Metrics

PDF: 25