Title: HGF/c-MET Targeted Therapeutics: Novel Strategies for Cancer Medicine
Volume: 12
Issue: 14
Author(s): Timothy A. Yap, Shahneen K. Sandhu, Salma M. Alam and Johann S. de Bono
Affiliation:
Keywords:
Hepatocyte growth factor, c-MET, targeted therapeutics, personalizd medicine, ARQ 197, MetMAb, monoclonal antibodies, small molecule inhibitors, clinical trials, cancer
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.
