Role of BET proteins in castration-resistant prostate cancer

Ester Fernandez-Salas; Shaomeng Wang; Arul M Chinnaiyan

doi:10.1016/j.ddtec.2016.07.001

Role of BET proteins in castration-resistant prostate cancer

Drug Discov Today Technol. 2016 Mar:19:29-38. doi: 10.1016/j.ddtec.2016.07.001. Epub 2016 Jul 30.

Authors

Ester Fernandez-Salas¹, Shaomeng Wang², Arul M Chinnaiyan³

Affiliations

¹ Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
² Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Medicinal Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
³ Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: arul@umich.edu.

PMID: 27769354
DOI: 10.1016/j.ddtec.2016.07.001

Abstract

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.

Publication types

Review

MeSH terms

Animals
Antineoplastic Agents / therapeutic use
Humans
Male
Nuclear Proteins / antagonists & inhibitors
Nuclear Proteins / metabolism*
Prostatic Neoplasms, Castration-Resistant / drug therapy
Prostatic Neoplasms, Castration-Resistant / metabolism*
Receptors, Androgen / metabolism
Signal Transduction
Transcription Factors / antagonists & inhibitors
Transcription Factors / metabolism*

Substances

Antineoplastic Agents
Nuclear Proteins
Receptors, Androgen
Transcription Factors