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[激酶抑制剂及其耐药性]

[Kinase inhibitors and their resistance].

作者信息

Togashi Yosuke, Nishio Kazuto

出版信息

Nihon Rinsho. 2015 Aug;73(8):1323-9.

Abstract

Kinase cascades are involved in all stages of tumorigenesis through modulation of transformation and differentiation, cell-cycle progression, and motility. Advances in molecular targeted drug development allow the design and synthesis of inhibitors targeting cancer-associated signal transduction pathways. Potent selective inhibitors with low toxicity can benefit patients especially with several malignancies harboring an oncogenic driver addictive signal. This article evaluates information on solid tumor-related kinase signals and inhibitors, including receptor tyrosine kinase or serine/threonine kinase signals that lead to successful application in clinical settings. In addition, the resistant mechanisms to the inhibitors is summarized.

摘要

激酶级联反应通过调节细胞转化与分化、细胞周期进程和运动性参与肿瘤发生的各个阶段。分子靶向药物研发的进展使得针对癌症相关信号转导通路的抑制剂得以设计和合成。具有低毒性的强效选择性抑制剂可使患者受益,尤其是对于几种携带致癌驱动成瘾信号的恶性肿瘤患者。本文评估了与实体瘤相关的激酶信号和抑制剂的信息,包括在临床环境中成功应用的受体酪氨酸激酶或丝氨酸/苏氨酸激酶信号。此外,还总结了抑制剂的耐药机制。

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