Bromodomain-containing proteins in prostate cancer

• Published in: Molecular and cellular endocrinology 2018-02, Vol.462 (Pt A), p.31-40
• Main Authors: Urbanucci, Alfonso, Mills, Ian G.
• Format: Article
• Language: English
• Subjects: Androgen receptor; Animals; BRD BET bromodomain and extra-terminal domain; BRD BET inhibitor; Chromatin - metabolism; Chromatin structure remodeling; Humans; Male; Nuclear Proteins - chemistry; Nuclear Proteins - metabolism; Prostate cancer; Prostatic Neoplasms - metabolism; Protein Domains; Receptors, Androgen - metabolism; Signal Transduction; Transcriptional co-activator
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2017.06.007

Several oncogenic factors have been involved in prostate cancer progression. However, therapeutic approaches still focus on suppression of androgen receptor (AR) signaling. In fact, whereas the full-length AR incorporates a ligand-binding domain, which has become a drug target for competitive inhibitors, other transcription factors often do not have tractable binding pockets that aid drug development. Consequently drug development efforts have turned to transcription co-regulators, often chromatin-modifying enzymes or factors that bind to epigenetic modifications to chromatin. Bromodomain (BRD)-containing proteins fall into the latter category and significant progress has been made in developing small molecule inhibitors that target a particular subgroup of BRD-containing proteins known as the Bromodomain and extra-terminal (BET) family proteins. These inhibitors have proven particularly effective in inactivating c-Myc in lymphoma but more recently members of the BET family have also been identified as AR-interacting proteins raising the prospect of using these inhibitors as an alternative strategy for targeting AR-driven cancers. In this review we will provide an overview of BRD-containing proteins and the potential for exploiting them as biomarkers and drug targets in prostate cancer. •Bromodomain-containing proteins (BRDs) regulate prostate cancer-specific transcriptional programs.•BRDs are androgen receptor co-activators and/or promote castration resistant growth.•BRDs genes are frequently altered in advanced prostate cancer cases.•Effective BRDs inhibitors are tested in clinical trials.•BRDs-targeted therapies will need better prognostication and stratification of patients.