c-Met as a Target for Personalized Therapy.
c-Met as a Target for Personalized Therapy.
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DOI：
10.4137/tog.s30534
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Peters GJ
中科院分区：
文献类型：
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作者：
Garajová I;Giovannetti E;Biasco G;Peters GJ
MET及其配体HGF参与了许多生理和病理的生物过程，使这一信号通路成为肿瘤学中一个有吸引力的治疗靶点。下游信号效应通过丝裂原活化蛋白激酶（MAPK）、PI3K（磷酸肌肽3-激酶蛋白激酶B）/AKT、转录蛋白信号转导和激活因子（STAT）、核因子-κB传递。这些通路的末端效应组分的最终输出是细胞质和核过程的激活，导致细胞增殖、存活、动员和侵袭能力的增加。除了其作为致癌驱动因素的作用外，越来越多的证据表明MET是对包括EGFR和VEGFR抑制剂在内的靶向治疗耐药的常见机制。在这篇综述中，我们总结了目前关于HGF-MET信号通路在癌症中的作用及其治疗靶点（HGF激活抑制剂、HGF抑制剂、MET拮抗剂和选择性/非选择性MET激酶抑制剂）的知识。本文讨论了该通路在当前肺癌、肾癌和胰腺癌抗癌策略的耐药性中的作用的最新进展。
MET and its ligand HGF are involved in many biological processes, both physiological and pathological, making this signaling pathway an attractive therapeutic target in oncology. Downstream signaling effects are transmitted via mitogen-activated protein kinase (MAPK), PI3K (phosphoinositide 3-kinase protein kinase B)/AKT, signal transducer and activator of transcription proteins (STAT), and nuclear factor-κB. The final output of the terminal effector components of these pathways is activation of cytoplasmic and nuclear processes leading to increases in cell proliferation, survival, mobilization and invasive capacity. In addition to its role as an oncogenic driver, increasing evidence implicates MET as a common mechanism of resistance to targeted therapies including EGFR and VEGFR inhibitors. In the present review, we summarize the current knowledge on the role of the HGF-MET signaling pathway in cancer and its therapeutic targeting (HGF activation inhibitors, HGF inhibitors, MET antagonists and selective/nonselective MET kinase inhibitors). Recent advances in understanding the role of this pathway in the resistance to current anticancer strategies used in lung, kidney and pancreatic cancer are discussed.