Role of BET proteins in castration-resistant prostate cancer

•CRPCs maintain and depend on AR signaling for survival.•BET bromodomain inhibitors inhibit AR signaling and regulate expression of wild-type, mutant and variant forms of AR.•BET-BRD proteins regulate oncogenic transcription factor mediated pathways including AR-, ERG- and c-Myc.•Pre-clinical testing of BET-BRD inhibitors in CRPC models has shown efficacy.•Clinical trials evaluating BET-BRD inhibitors as single agent and in combination with enzalutamide hold promise in the treatment of CRPC.

Castration resistant prostate cancer (CRPC) is a deadly disease with few therapeutic options once patients become resistant to second generation drugs targeting the AR-transcriptional program. The BET-BRD readers of chromatin are key regulators of AR-, ERG-, and c-Myc-mediated transcription in CRPC. BET-BRD inhibitors have demonstrated pre-clinical efficacy in models of CRPC and are currently being evaluated in several clinical trials. These novel drugs have the potential to transform the way we treat CRPC in the near future.