The BCL-2 arbiters of apoptosis and their growing role as cancer targets

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…

• VC
  Victorian Cancer Agency
• AC
  Australian Cancer Research Foundation
• MR
  Medical Research Council

  Awards: 1016701, 461221
• NH
  National Health and Medical Research Council

  Awards: 461221, 1016647, 1016701, 1079560, 9000220
• CC
  Cancer Council Victoria

  Award: 461221