Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Biol Ther. 2012 Mar;13(5):237-8. doi: 10.4161/cbt.19608. Epub 2012 Mar 1.

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

Author information

1
Molecular Pharmacology Section, Medical Oncology Branch, National Cancer Institute, Bethesda, MD, USA.

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.

PMID:
22336886
PMCID:
PMC3367713
DOI:
10.4161/cbt.19608
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis Icon for PubMed Central
    Loading ...
    Support Center