Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies

Nat Rev Cancer. 2016 Feb;16(2):99-109. doi: 10.1038/nrc.2015.17.


The 'hallmarks of cancer' are generally accepted as a set of genetic and epigenetic alterations that a normal cell must accrue to transform into a fully malignant cancer. It follows that therapies designed to counter these alterations might be effective as anti-cancer strategies. Over the past 30 years, research on the BCL-2-regulated apoptotic pathway has led to the development of small-molecule compounds, known as 'BH3-mimetics', that bind to pro-survival BCL-2 proteins to directly activate apoptosis of malignant cells. This Timeline article focuses on the discovery and study of BCL-2, the wider BCL-2 protein family and, specifically, its roles in cancer development and therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biphenyl Compounds / pharmacology
  • Cell Death
  • Gene Expression Regulation, Neoplastic
  • Genes, bcl-2
  • Humans
  • Mice
  • Mitochondrial Membrane Transport Proteins
  • Molecular Targeted Therapy / methods*
  • Multigene Family
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Nitrophenols / pharmacology
  • Piperazines / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sulfonamides / pharmacology
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • ABT-737
  • Biphenyl Compounds
  • Mitochondrial Membrane Transport Proteins
  • Nitrophenols
  • Piperazines
  • Proto-Oncogene Proteins c-bcl-2
  • RTL10 protein, human
  • Sulfonamides
  • bcl-2-Associated X Protein