Bromodomain-containing proteins in prostate cancer

Abstract

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.

Keywords: Androgen receptor; BRD BET bromodomain and extra-terminal domain; BRD BET inhibitor; Chromatin structure remodeling; Prostate cancer; Transcriptional co-activator.