The BCL-2 arbiters of apoptosis and their growing role as cancer targets
Jerry M Adams, Suzanne Cory
CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 2018
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 fo..View full abstract
Awarded by National Health and Medical Research Council
Awarded by SCOR grants from the Leukemia & Lymphoma Society
Awarded by government of Australia (IRIISS)
We warmly thank our colleagues at the Walter and Eliza Hall Institute (WEHI) and elsewhere for their many contributions to the research and ideas underpinning this review and apologise to any colleagues whose findings could not be cited because of space constraints. Work in the authors' laboratories was supported by fellowship and grants from the National Health and Medical Research Council (461221, 1016701, 1016647, 1079560, 1041797); SCOR grants (7001-15) from the Leukemia & Lymphoma Society; and support from the Victorian Cancer Agency, the Cancer Council Victoria; and the Australian Cancer Research Foundation. Research infrastructure at WEHI is supported by annual grants from the governments of Australia (IRIISS Grant 9000220) and Victoria (OIS grant).