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Novel Androgen Inhibitors Offer Promise in Treatment of Prostate Cancer
Castration has long been the primary strategy for the treatment of metastatic prostate cancer. Prostatic tumors need androgenic hormones to grow, and until now, efforts to chemically block all of these hormones have proven disappointing. However, researchers at the University of Maryland School of Medicine have identified new androgen inhibitors that they believe could supplant castration as the primary method of treatment for prostate cancer.
Dr. Angela Brodie, professor of pharmacology and experimental therapeutics, and research fellow Yang-zhi Ling, believe that several inhibiting compounds discovered in their research show promise as both first-line and complementary treatments of prostate cancer.
"It's been known for some time that total androgen inhibition could be more effective than castration, but we hadn't been able to identify and synthesize a compound that would suppress both testicular and adrenal androgens," said Brodie. "Despite removal of the testes, some prostatic tumors can be stimulated even by very low levels of androgens, and some adapt well enough to convert adrenal androgen into a stronger androgen called DHT. These compounds show promise of a more thorough blockade, even against these more difficult tumors, than any we've seen before."
The growth of human prostatic tumors is dependent on the presence of androgens, and the testes are the primary synthesis site of the androgen testosterone. Patients who undergo castration frequently relapse because the adrenal gland produces low levels of androgens sufficient to stimulate tumor growth. Tumor cells can also convert these androgens into dihydrotestosterone (DHT), a particularly powerful androgenic hormone. Recent research by the National Cancer Institute suggests that efforts to block the effects of adrenal androgens would result in worthwhile therapeutic gains, but current therapies have shown limited efficacy in clinical trials and can cause undesirable side-effects. Brodie expects to see completion of toxicology tests in six months, commencement of phase one human trials soon after.
"I had no doubt of the importance of evaluating these potential new therapies," said Brodie. "We hope these new inhibitors will prove to be more effective than current treatments in limiting the growth of tumors."
According to the 1997 American Cancer Society Facts and Figures, prostate cancer will account for approximately 334,500 new cases and 41,800 deaths this year.
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