Liu Xiangdong, Yao Wenqing, Newton Robert C, Scherle Peggy A
Incyte Corporation, Experimental Station, Rt. 141 & Henry Clay Road, Wilmington, DE 19880, USA.
Expert Opin Investig Drugs. 2008 Jul;17(7):997-1011. doi: 10.1517/13543784.17.7.997.
In many human cancers, c-MET is activated via receptor overexpression, amplification, mutation and/or a ligand-dependent autocrine/paracrine loop. These biochemical and genetic abnormalities have been correlated with poor clinical outcomes and drug resistance in cancer patients. Preclinical studies suggest that targeting aberrant c-MET signaling could be an attractive therapy in cancer, but this notion has only recently been tested in the clinic.
To describe the biological aspects of the c-MET signaling pathway and to discuss recent progress and possible future trends in the development of agents that target the c-MET pathway, with an emphasis on small-molecule c-MET kinase inhibitors.
A review of relevant publications, including published articles in literature, reports at scientific meetings, and information available through the Internet.
RESULTS/CONCLUSION: The dysregulated c-MET pathway represents a promising target for cancer drug development. The agents that target the c-MET pathway have demonstrated impressive evidence of early clinical activity and may have a significant therapeutic potential.
在许多人类癌症中，c-MET通过受体过表达、扩增、突变和/或配体依赖性自分泌/旁分泌环被激活。这些生化和基因异常与癌症患者的不良临床结局和耐药性相关。临床前研究表明，靶向异常的c-MET信号传导可能是一种有吸引力的癌症治疗方法，但这一概念直到最近才在临床上得到验证。
描述c-MET信号通路的生物学特性，并讨论靶向c-MET通路药物开发的最新进展和未来可能的趋势，重点是小分子c-MET激酶抑制剂。
对相关出版物进行综述，包括文献中的发表文章、科学会议报告以及通过互联网获取的信息。
结果/结论：失调的c-MET通路是癌症药物开发的一个有前景的靶点。靶向c-MET通路的药物已显示出令人印象深刻的早期临床活性证据，可能具有显著的治疗潜力。
