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.
Original language | English (US) |
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Pages (from-to) | 2045-2058 |
Number of pages | 14 |
Journal | Current Drug Targets |
Volume | 12 |
Issue number | 14 |
DOIs | |
State | Published - Dec 1 2011 |
Externally published | Yes |
Keywords
- ARQ 197
- c-MET
- Clinical trials
- Hepatocyte growth factor
- MetMAb
- Monoclonal antibodies
- Personalized medicine
- Small molecule inhibitors
- Targeted therapeutics
ASJC Scopus subject areas
- Drug Discovery
- Pharmacology
- Clinical Biochemistry
- Molecular Medicine