关键词： ASH, American Society of Hematology ATAP, amphipathic tail-anchoring peptide Apoptosis BAD, BCL-2-associated death promoter protein BAK, BCL-2 homologous antagonist killer BAX, BCL-2-associated X protein BCL-2 family BCL-2, B-cell lymphoma 2 BCL-w (BCL2L2), BCL-2-like protein 2 BCL-xL, B-cell lymphoma X long BCR, B-cell receptor BFL-1 (BCL2A1), BCL-2-related protein A1 BH3 profiling BH3, BCL-2 homology 3 BID, BH3 interacting domain death agonist BIK, BCL-2-interacting killer BIM, BCL-2-interacting mediator of cell death BOK, BCL-2 related ovarian killer BTK, Bruton׳s tyrosine kinase CDK, cyclin-dependent kinase CHOP, cyclophosphamide, hydroxydaunorubicin, oncovin-vincristine and prednisone CLL, chronic lymphocytic leukemia CML, chronic myelogenous leukemia CR, complete response;EGFR, epidermal growth factor receptor Combination therapy ER, endoplasmic reticulum ERK, extracellular signal-regulated kinase FDA, U. S. Food and Drug Administration GSK-3, glycogen synthase kinase-3 ITK, interleukin-2-inducible T-cell kinase MCL, myeloid cell leukemia MOMP, mitochondrial outer membrane permeabilization Mitochondrial priming NHL, non-Hodgkin lymphoma NIH, National Institutes of Health NSCLC, non-small cell lung cancer PI3K, phosphatidylinositol-3-kinase PUMA, p53 up-regulated modulator of apoptosis SLL, small lymphocytic lymphoma T-ALL, T-acute lymphocytic leukemia Targeted therapy

来  源：   DOI：10.1016/j.apsb.2016.08.005   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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.
摘要：
细胞凋亡,尤其是内在的线粒体细胞死亡途径，受BCL-2家族蛋白调控。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。靶向凋亡缺陷，通过直接抑制BCL-2家族蛋白或通过调节途径，可以恢复细胞对细胞死亡的敏感性。这篇综述将集中在BCL-2家族蛋白的方面，它们与激酶通路的相互作用，以及新型靶向药物如何帮助克服凋亡障碍。此外，功能测定，例如BH3配置文件，可能有助于预测对化学疗法的反应，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。
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