Incyte Corporation, Experimental Station, Wilmington, DE 19880, USA.
Trends Mol Med. 2010 Jan;16(1):37-45. doi: 10.1016/j.molmed.2009.11.005. Epub 2009 Dec 22.
Successfully developed target-based therapies have significantly changed cancer treatment. Among many targets, the c-MET receptor tyrosine kinase and its ligand hepatocyte growth factor have recently gained considerable attention. The c-MET pathway is dysregulated in most human malignancies, and regulates tumor formation, progression and dissemination, and numerous c-MET pathway inhibitors are currently being evaluated in the clinic. Although some studies have shown impressive evidence of antitumor activity, the data should be interpreted with caution because of the distinct properties of these agents and diverse patient populations studied. Furthermore, in tumor types where patients might benefit from c-MET inhibition, rational combination treatments might ultimately provide maximal clinical benefit. Here, we review the evidence linking c-MET activation to cancer, and discuss the latest progress, opportunities and challenges in the clinical development of c-MET pathway inhibitors.
靶向治疗的成功发展显著改变了癌症治疗。在众多靶点中，c-MET 受体酪氨酸激酶及其配体肝细胞生长因子最近引起了相当大的关注。c-MET 通路在大多数人类恶性肿瘤中失调，调节肿瘤的形成、进展和扩散，目前正在临床评估许多 c-MET 通路抑制剂。尽管一些研究显示出了令人印象深刻的抗肿瘤活性证据，但由于这些药物的独特性质和研究的不同患者群体，数据应谨慎解释。此外，在可能受益于 c-MET 抑制的肿瘤类型中，合理的联合治疗最终可能提供最大的临床获益。在这里，我们回顾了 c-MET 激活与癌症的关联证据，并讨论了 c-MET 通路抑制剂临床开发的最新进展、机遇和挑战。
