The BCL-2 arbiters of apoptosis and their growing role as cancer targets
AuthorAdams, JM; Cory, S
Source TitleCell Death and Differentiation
PublisherNATURE PUBLISHING GROUP
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsAdams, J. M. & Cory, S. (2018). The BCL-2 arbiters of apoptosis and their growing role as cancer targets. CELL DEATH AND DIFFERENTIATION, 25 (1), pp.27-36. https://doi.org/10.1038/cdd.2017.161.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729526
Impaired apoptosis plays a central role in cancer development and limits the efficacy of conventional cytotoxic therapies. Deepening understanding of how opposing factions of the BCL-2 protein family switch on apoptosis and of their structures has driven development of a new class of cancer drugs that targets various pro-survival members by mimicking their natural inhibitors, the BH3-only proteins. These 'BH3 mimetic' drugs seem destined to become powerful new weapons in the arsenal against cancer. Successful clinical trials of venetoclax/ABT-199, a specific inhibitor of BCL-2, have led to its approval for a refractory form of chronic lymphocytic leukaemia and to scores of on-going trials for other malignancies. Furthermore, encouraging preclinical studies of BH3 mimetics that target other BCL-2 pro-survival members, particularly MCL-1, offer promise for cancers resistant to venetoclax. This review sketches the impact of the BCL-2 family on cancer development and therapy, describes how interactions of family members trigger apoptosis and discusses the potential of BH3 mimetic drugs to advance cancer therapy.
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