From the Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
Author's disclosure of potential conflicts of interest is found at the end of this article.
Address reprint requests to Ravi Salgia, MD, PhD, Director, Thoracic Oncology Research Program, 5841 South Maryland Ave, Chicago, IL 60637; E-mail: rsalgia{at}medicine.bsd.uchicago.edu
Overview: c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are important in many biologic functions in malignant cells, including cell proliferation, reduced apoptosis, altered cytoskeletal functions, epithelial-mesenchymal transition, and increased metastasis. Specific mutations and amplification of c-Met have been seen in many solid tumors. The tyrosine kinase domain, juxtamembrane domain, or semaphorin domain of c-Met have been shown to be mutated (germline and/or somatic). c-Met gain-of-function mutations lead to deregulated or prolonged tyrosine kinase activity — instrumental to its transforming activity. This article reviews the different biologic functions regulated by c-Met, the structural requirements, and the development of HGF and c-Met as therapeutic targets in preclinical and clinical trials. Targeting the c-Met pathway, alone or in combined with standard therapies, is likely to improve current therapies in c-Met–dependent malignancies.
