The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy

Cell Death Differ. 2011 Sep;18(9):1414-24. doi: 10.1038/cdd.2011.17. Epub 2011 Mar 18.


Tumour development requires a combination of defects that allow nascent neoplastic cells to become self-sufficient for cell proliferation and insensitive to signals that normally restrain cell growth. Among the latter, evasion of programmed cell death (apoptosis) has proven to be critical for the development and sustained growth of many, perhaps all, cancers. Apoptotic cell death is regulated by complex interactions between pro-survival members and two subgroups of pro-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family. In this invited review article, we reminisce on the discovery of Bcl-2, the first regulator of cell death identified, we discuss the mechanisms that control apoptotic cell death, focussing on how defects in this process promote the development and sustained growth of tumours and also affect their responses to anticancer therapeutics and, finally, we describe how current knowledge of the regulatory networks of apoptosis is exploited to develop novel approaches for cancer therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Humans
  • Mice
  • Minor Histocompatibility Antigens
  • Molecular Targeted Therapy
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / physiology*


  • Antineoplastic Agents
  • BCL2-related protein A1
  • Minor Histocompatibility Antigens
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2