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Progress in cancer therapy targeting c-Met signaling pathway

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A primary hurdle in developing anticancer therapeutics is to selectively target cancer cells while sparing normal tissues. Oncogenic protein kinases represent a class of biologically important targets for cancer intervention. Among them, c-Met is a receptor tyrosine kinase (RTK) that has low activity in normal tissues but is dysregulated in many tumor types. The c-Met is the prototype member of a subfamily of RTKs, which includes Ron, which is structurally distinct from other RTK families. It is the only known high-affinity receptor for hepatocyte growth factor, also known as scatter factor. HGF and c-Met are both required for normal mammalian development. In adults, both are widely expressed in a variety of tissues; however, their expression is normally very low and is involved mainly in tissue damage, repair and regeneration. The results of in vitro and in vivo experiments have shown that this receptor-growth factor pair is involved in multiple physiologic cellular responses, including cell proliferation, survival, differentiation, motility, and invasion. Here, as well as presenting the biological aspects of c-Met signaling regulation, we consider recent findings that have provided new knowledge at the molecular, cellular, and animal study. Also, we describe how the c-Met pathway is tuned by the functional cooperation between various signal transducers. We then discuss the progress in the development of agents that target the c-Met pathway, with an emphasis on small molecules of c-Met kinase inhibitors. Finally, we provide our perspective in terms of possible future trends and limitation in this field.

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  1. Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, 400-712, Korea

    Kyung Hee Jung, Byung Hee Park & Soon-Sun Hong

  2. College of Medicine, Inha Unversity, Incheon, 400-712, Korea

    Soon-Sun Hong

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Jung, K.H., Park, B.H. & Hong, SS. Progress in cancer therapy targeting c-Met signaling pathway. Arch. Pharm. Res. 35, 595–604 (2012). https://doi.org/10.1007/s12272-012-0402-6

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