How to unleash mitochondrial apoptotic blockades to kill cancers?
How to unleash mitochondrial apoptotic blockades to kill cancers?
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DOI：
10.1016/j.apsb.2016.08.005
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Deng J
中科院分区：
文献类型：
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作者：
Deng J
细胞凋亡，尤其是固有的线粒体细胞死亡途径，是由BCL-2蛋白家族调控的。细胞凋亡机制的缺陷是细胞逃避细胞死亡和癌变的主要机制之一。无论是通过直接抑制BCL-2家族蛋白，还是通过调节调控途径，靶向细胞凋亡缺陷，都可以恢复细胞对死亡的敏感性。这篇综述将集中在BCL-2家族蛋白的方面，它们与激酶途径的相互作用，以及新的靶向药物如何帮助克服凋亡阻断。此外，功能分析，如BH3谱分析，可能有助于预测对化疗的反应，并通过确定启动细胞死亡的线粒体阈值来帮助选择联合疗法。逃避细胞凋亡是癌细胞的一个特征。如何通过直接抑制BCL-2家族蛋白或间接调节其他促进生存的信号通路来攻击凋亡缺陷，是现代癌症治疗面临的挑战。幸运的是，在应对这一挑战方面已经取得了很大进展。
Apoptosis, especially the intrinsic mitochondrial cell death pathway, is regulated by the BCL-2 family of proteins. Defects in apoptotic machinery are one of the main mechanisms that cells employ to evade cell death and become cancerous. Targeting the apoptotic defects, either by direct inhibition of BCL-2 family proteins or through modulation of regulatory pathways, can restore cell sensitivity to cell death. This review will focus on the aspects of BCL-2 family proteins, their interactions with kinase pathways, and how novel targeted agents can help overcome the apoptotic blockades. Furthermore, functional assays, such as BH3 profiling, may help in predicting responses to chemotherapies and aid in the selection of combination therapies by determining the mitochondrial threshold for initiating cell death. Evading apoptosis is a hallmark of cancer cells. How to attack the apoptotic defects, through direct inhibition of BCL-2 family proteins or by indirect regulation of other promoting survival signaling pathways, is the challenge for modern cancer therapies. Fortunately, a lot of progress has been made to meet that challenge.