|
KMID : 0043320120350040595
|
|
Archives of Pharmacal Research
2012 Volume.35 No. 4 p.595 ~ p.604
|
|
|
Progress in cancer therapy targeting c-Met signaling pathway
|
|
Jung Kyung-Hee
Park Byung-Hee
Hong Soon-Sun
|
|
|
Abstract
|
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Cancerc-Met, Hepatocyte growth factor (HGF), Receptor tyrsine kinase, Cancer drug development, Proliferation, Signal transduction
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|