Dihydrotestosterone synthesis from adrenal precursors does not involve testosterone in castration-resistant prostate cancer

Tessa J. Campbell, Donald J. Tindall, William D. Figg

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Androgen deprivation therapy is the frontline treatment for metastatic prostate cancer; however, because the majority of cases of advanced prostate cancer progress to castration-resistant prostate cancer (CRPC), there is a considerable need to better understand the synthesis of intratumoral concentrations of the androgen receptor (AR) agonist, 5α- dihydrotestosterone (DHT) in CRPC. In a recent article in the Proceedings of the National Academy of Sciences, Chang et al. show that, contrary to widely held assumptions, the dominant pathway to DHT synthesis does not involve testosterone as a precursor to DHT, but instead involves the conversion of Δ 4-androstenedione (AD) to 5α-dione (AD→5α dione→DHT) by the steroid-5α-reductase isoenzyme 1 (SRD5A1). The authors show that it is this alternative pathway that drives the progression of CRPC, and they confirm these findings in six established human prostate cancer cell lines as well as in the metastatic tumors from two patients with CRPC. Such findings open the door to new areas of research and to the development of new therapeutic targets in CRPC.

Original languageEnglish (US)
Pages (from-to)237-238
Number of pages2
JournalCancer Biology and Therapy
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2012

Fingerprint

Dihydrotestosterone
Castration
Testosterone
Prostatic Neoplasms
Androgens
Androstenedione
Isoenzymes
Oxidoreductases
Therapeutics
Steroids
Cell Line
Research

Keywords

  • Δ - androstenedione
  • 5α-dione
  • DHEA
  • DHT
  • Prostate cancer
  • SRD5A1
  • Testosterone

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Dihydrotestosterone synthesis from adrenal precursors does not involve testosterone in castration-resistant prostate cancer. / Campbell, Tessa J.; Tindall, Donald J.; Figg, William D.

In: Cancer Biology and Therapy, Vol. 13, No. 5, 01.03.2012, p. 237-238.

Research output: Contribution to journalArticle

Campbell, Tessa J. ; Tindall, Donald J. ; Figg, William D. / Dihydrotestosterone synthesis from adrenal precursors does not involve testosterone in castration-resistant prostate cancer. In: Cancer Biology and Therapy. 2012 ; Vol. 13, No. 5. pp. 237-238.
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