Targeting BET bromodomains for cancer treatment

Epigenomics. 2015;7(3):487-501. doi: 10.2217/epi.14.91.

Abstract

The bromodomain and extraterminal (BET) subfamily of bromodomain-containing proteins has emerged in the last few years as an exciting, novel target group. BRD4, the best studied BET protein, is implicated in a number of hematological and solid tumors. This is linked to its role in modulating transcription elongation of essential genes involved in cell cycle and apoptosis such as c-Myc and BCL2. Potent BET inhibitors with promising antitumor efficacy in a number of preclinical cancer models have been identified in recent years. This led to clinical studies focusing mostly on the treatment of leukemia and lymphoma, and first encouraging signs of efficacy have already been reported. Here we discuss the biology of BRD4, its known interaction partners and implication in different tumor types. Further, we summarize the current knowledge on BET bromodomain inhibitors.

Keywords: BET inhibitor; BRD4; bromodomain; c-Myc; chromatin; transcription control.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Cycle Proteins
  • Hematologic Neoplasms / drug therapy
  • Humans
  • Mice
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • Protein Structure, Tertiary
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism
  • Transcription Factors / physiology

Substances

  • Antineoplastic Agents
  • BRD4 protein, human
  • Cell Cycle Proteins
  • Nuclear Proteins
  • Transcription Factors