How to unleash mitochondrial apoptotic blockades to kill cancers?

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• 作者：Jing Deng ^{jing_deng@dfci.harvard.edu}
• 关键词：ASH ; American Society of Hematology ; ATAP ; amphipathic tail-anchoring peptide ; BAD ; BCL-2-associated death promoter protein ; BAK ; BCL-2 homologous antagonist killer ; BAX ; BCL-2-associated X protein ; BCL-2 ; B-cell lymphoma 2 ; BCL-w (BCL2L2) ; BCL-2-like protein 2 ; BCL-xL ; B-cell lymphoma X long ; BFL-1 (BCL2A1) ; BCL-2-related protein A1 ; BCR ; B-cell receptor ; BH3 ; BCL-2 homology 3 ; BID ; BH3 interacting domain death agonist ; BIK ; BCL-2-interacting killer ; BIM ; BCL-2-interacting mediator of cell deat
• 刊名：Acta Pharmaceutica Sinica B
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：7
• 期：1
• 页码：18-26
• 全文大小：811 K
• 卷排序：7

文摘

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.