Delineation of the androgen-regulated signaling pathways in prostate cancer facilitates the development of novel therapeutic approaches

Curr Opin Pharmacol. 2018 Aug:41:1-11. doi: 10.1016/j.coph.2018.03.002. Epub 2018 Mar 30.

Abstract

Although androgen deprivation therapy (ADT) is initially effective for the treatment of progressive prostate cancer, it inevitably fails due to the onset of diverse resistance mechanisms that restore androgen receptor (AR) signaling. Thus, AR remains a desired therapeutic target even in the relapsed stages of the disease. Given the difficulties in stopping all AR reactivation mechanisms, we propose that the identification of the driver signaling events downstream of the receptor offer viable, alternative therapeutic targets. Here, we summarize recently described, AR-regulated processes that have been demonstrated to promote prostate cancer. By highlighting these signaling events and describing some of the ongoing efforts to pharmacologically modulate these pathways, our goal is to advocate potential new therapeutic targets that would represent an alternative approach for blocking AR actions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Androgens* / genetics
  • Androgens* / metabolism
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Signal Transduction / drug effects

Substances

  • Androgen Antagonists
  • Androgens