Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects

Oncogene. 2015 Apr 2;34(14):1745-57. doi: 10.1038/onc.2014.115. Epub 2014 May 19.

Abstract

Androgen receptor (AR) signaling is a critical pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. However, over time, most tumors become resistant to ADT. The view of castration-resistant prostate cancer (CRPC) has changed dramatically in the last several years. Progress in understanding the disease biology and mechanisms of castration resistance led to significant advancements and to paradigm shift in the treatment. Accumulating evidence showed that prostate cancers develop adaptive mechanisms for maintaining AR signaling to allow for survival and further evolution. The aim of this review is to summarize molecular mechanisms of castration resistance and provide an update in the development of novel agents and strategies to more effectively target the AR signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androstenes / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • DNA Damage / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Humans
  • Male
  • Phenylthiohydantoin / analogs & derivatives
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / genetics
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism*
  • Response Elements / genetics
  • Signal Transduction

Substances

  • AR protein, human
  • Androstenes
  • Antineoplastic Agents
  • MDV 3100
  • Receptors, Androgen
  • Phenylthiohydantoin
  • abiraterone