Review of Clinic Trials: Agents Targeting c-Met
Oyewale Abidoye, Nadh Murukurthy and Ravi Salgia
Affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago Medical Center, Pritzker School of Medicine, 5841 South Maryland Avenue, MC 2115, Chicago, IL 60637.
Receptor tyrosine kinases are a group of molecules that can enhance cellular proliferation, cell motility and migration, and eventual metastasis. c-Met receptor tyrosine kinase has a significant biological and biochemical effect on cancer cells, and appears to be an important therapeutic target. In many cancers, c-Met (which can be activated by its ligand hepatocyte growth factor, HGF) can be overexpressed, activated, amplified, and/or mutated. The mutations of c-Met had initially been described in the tyrosine kinase domain, and we have described them in other “hot-spots” such as the juxtamembrane and semaphorin domains. Targeting c-Met has been very fruitful pre-clinically, and currently, there are several clinical trials for advanced cancers. Described in this review are some of the biological and biochemical aspects of c-Met, and detailed are a number of therapeutic strategies. With our understanding of c-Met biology and role in cancer, we should be able to arrive at a unique strategy to eradicate cancers in which c-Met plays a significant role.
Keywords: Hepatocyte growth factor, c-Met receptor tyrosine kinase, RTK catalytic activity, mTOR pathway, XL184
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