Targeting BET Bromodomains for Cancer Treatment

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
• chromatin
• c-Myc
• transcription control

Financial & competing interests disclosure

All authors are employees of Bayer Pharma AG, which has a commercial interest in the development of BET inhibitors. A Fernández-Montalván, S Siegel and B Haendler are co-inventors of several patent applications related to BET inhibitors and own shares of Bayer AG. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

We thank the numerous colleagues involved in chromatin modulation projects for many helpful discussions.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.