Blocking Androgen Synthesis May Reverse Advanced Prostate Cancer

Advanced prostate cancer becomes resistant to hormone therapy when tumor cells begin independently to synthesize their own androgens in a metabolic sequence that may be blocked by a new generation of chemotherapeutic agents.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) worked with prostate cancer cell lines that had been taken from patients with castration-resistant prostate cancer (CRPC). CRPC continues to be driven by testosterone or dihydrotestosterone obtained in part from intratumoral synthesis. This mechanism requires the 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) metabolism of delta-5-steroids, including dehydroepiandrosterone (DHEA) and delta-5-androstenediol (A5diol), to testosterone.

In a study published in the August 2010 issue of the journal Endocrinology the investigators reported that tumor growth could be suppressed by using known inhibitors of 3-beta-HSD.

"We were able to block the androgen response, which is a central pathway for tumor progression,” said senior author Dr. Nima Sharifi, assistant professor of internal medicine at the University of Texas Southwestern Medical Center. "Enzymes in general can make great drug targets, so this process conceivably could be targeted for the development of new treatments for end-stage prostate cancer, which has limited therapeutic options right now. The goal would be to develop a drug that targets that enzyme to be used for the advanced, incurable stage. No standard treatments currently target this enzyme, but there is proven clinical evidence that this pathway is central to driving tumor progression.”

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University of Texas Southwestern Medical Center