B-Raf和MEK抑制剂获得性耐药机制及应对策略
首发时间:2014-10-28
摘要:近十年来,针对癌症中过度激活的MAPK通路已成功研发了许多B-Raf和MEK抑制剂,部分化学结构已经进入了临床研究,取得了显著疗效。然而,几乎所有的患者在7-8个月有效期后病情复发,发展为B-Raf和MEK抑制剂获得性耐药患者。本文首先简要介绍目前临床研究的代表性B-Raf和MEK抑制剂,重点阐释获得性耐药机制,最后基于其耐药机制列举目前克服临床耐药的研究方向。
关键词: B-Raf抑制剂 MEK抑制剂 耐药性 联合用药 抗肿瘤
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Acquired mechanism of B-Raf/MEK inhibitors and strategies to overcome it
Abstract:In the past decades, dozens of B-Raf and MEK inhibitors targeting MAPK pathway have been developed, with several chemical agents entered clinical trials and obtained outstanding therapeutic efficacy. After 7-8 months of clinical responses however, almost all of treated patients relapse and become acquired resistance. In this review, the clinical studied B-Raf and MEK inhibitors will be first described, with the focus on the mechanism of acquired resistance. The future research direction of how to overcome acquired resistance will also be outlined.
Keywords: B-Raf inhibitor MEK inhibitor drug resistance combination therapy antitumor
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No.4613934631911141****
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