BCL-2 Family Antagonists for Cancer Therapy

Nat Rev Drug Discov. 2008 Dec;7(12):989-1000. doi: 10.1038/nrd2658.

Abstract

Overexpression of members of the BCL-2 family of pro-survival proteins is commonly associated with unfavourable pathogenesis in cancer. The convergence of cytotoxic stress signals on the extended BCL-2 protein family provides the biological rationale for directly targeting this family to induce apoptotic cell death. Recently, several compounds have been described that inhibit the interaction between BCL-2 family members and their natural ligand, a helical peptide sequence known as the BH3 domain. Here, we review preclinical and clinical data on these compounds, and recommend four criteria that define antagonists of the BCL-2 protein family.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Cell Death / drug effects*
  • Cell Survival / drug effects
  • Drug Design
  • Humans
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / genetics
  • Models, Animal
  • Models, Molecular
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Protein Conformation
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • bcl-2-Associated X Protein / drug effects

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein