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Updated: Oct 16, 2025

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BET Proteins as Attractive Targets for Cancer Therapeutics

Joanna Sarnik1, Tomasz Popławski2, Paulina Tokarz2

  • 1Department of Rheumatology, Medical University of Lodz, 90-050 Lodz, Poland.

International Journal of Molecular Sciences
|October 23, 2021
PubMed

Insights

Bromodomain and extraterminal domain (BET) inhibitors show promise in cancer therapy by disrupting gene expression. Combining BET inhibitors with PARP inhibitors triggers synthetic lethality, offering a novel approach for epigenome and transcriptome cancer treatment.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Transcriptional dysregulation is a key driver of cancer initiation and progression.
  • Cancer cells can become dependent on specific gene expression regulators.
  • Bromodomain and extraterminal domain (BET) proteins are epigenetic readers involved in carcinogenesis.

Purpose of the Study:

  • To evaluate the potential of BET inhibitors (BETis) as anticancer agents.
  • To explore the efficacy of BETis in combination with other therapeutic agents.
  • To elucidate the mechanisms underlying BETis' anticancer activity.

Main Methods:

  • Review of Phase I and II clinical trials for BETis.
  • Preclinical evaluation of BETis in combination with DNA repair inhibitors.
  • Mechanistic studies on the interaction of BETis with homologous recombination pathway proteins.

Main Results:

  • BETis demonstrated potential but had limited success as monotherapies due to toxicities and resistance.
  • BETis synergized with DNA repair inhibitors, including PARP inhibitors, in preclinical models.
  • BETis were found to target key homologous recombination proteins like RAD51, BRCA1, and CtIP.

Conclusions:

  • BET inhibitors offer a novel therapeutic strategy targeting the epigenome and transcriptome in cancer.
  • Combination therapy, particularly with PARP inhibitors, shows promise for overcoming limitations of BETis monotherapy.
  • Further research is needed to fully understand the mechanisms and optimize the clinical application of BETis.
Keywords:
BETBETiDNA repaircancerhomologous recombinationtranscription

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