BET bromodomain inhibitors-A novel epigenetic approach in castration-resistant prostate cancer

Sarah E. Lochrin, Douglas K. Price, William D. Figg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The androgen receptor (AR) is central to the initiation and progression of prostate cancer, even after castration. There has been some success in therapies targeting AR signaling which have been shown to extend survival in men with castrationresistant prostate cancer (CRPC). However, durable responses to these therapies have been limited and there is a need to identify additional therapeutic targets within the AR-signaling network. Recently a group at University of Michigan Medical School outlined the potential for BET bromodomain protein inhibitors as a novel epigenetic approach to treatment of CRPC. In prostate cancer cell lines, BET bromodomain inhibitor, JQ1, was shown to induce apoptosis and down-regulate AR-regulated gene transcription. Bromodomain and the extra-terminal (BET) subfamily of human bromodomain proteins, with a focus on BRD4, were shown to play a major role in AR signaling and interact with AR via bromodomain (BD) 1/2. JQ1 inhibits this BRD4-AR bond, resulting in removal of RNA polymerase II from AR target genes, causing reduced ARgene transcription and subsequent diminished AR signaling. JQ1 lead to a significant reduction in tumor volume and weight in VCaP xenograftmice.

Original languageEnglish
Pages (from-to)1583-1585
Number of pages3
JournalCancer Biology and Therapy
Issue number12
StatePublished - 1 Dec 2014
Externally publishedYes


  • Androgen receptor
  • Bet bromodomain inhibitor
  • Castration-resistant prostate cancer
  • Gene transcription


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