Targeting MET in cancer: rationale and progress

被引:1206
作者
Gherardi, Ermanno [1 ,2 ]
Birchmeier, Walter [3 ]
Birchmeier, Carmen [3 ]
Woude, George Vande [4 ]
机构
[1] Med Res Council MRC Ctr, Cambridge CB2 2QH, England
[2] Univ Pavia, Div Immunol & Gen Pathol, Dept Mol Med, I-27100 Pavia, Italy
[3] Max Delbruck Ctr Mol Med MDC, D-13125 Berlin, Germany
[4] Van Andel Res Inst, Grand Rapids, MI 49503 USA
关键词
HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; FACTOR SCATTER FACTOR; FACTOR ACTIVATOR INHIBITOR; SMALL-MOLECULE INHIBITOR; SIGNAL-REGULATED KINASE; C-MET; FACTOR/SCATTER FACTOR; STEM-CELLS; CRYSTAL-STRUCTURE;
D O I
10.1038/nrc3205
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Uncontrolled cell survival, growth, angiogenesis and metastasis are essential hallmarks of cancer. Genetic and biochemical data have demonstrated that the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the tyrosine kinase MET, have a causal role in all of these processes, thus providing a strong rationale for targeting these molecules in cancer. Parallel progress in understanding the structure and function of HGF/SF, MET and associated signalling components has led to the successful development of blocking antibodies and a large number of small-molecule MET kinase inhibitors. In this Review, we discuss these advances, as well as results from recent clinical studies that demonstrate that inhibiting MET signalling in several types of solid human tumours has major therapeutic value.
引用
收藏
页码:89 / 103
页数:15
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