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Research Explains How Advanced Prostate Cancer Becomes Resistant to Androgen-Deprivation Therapy
Date:6/2/2008

bitors of enzymes that perform subsequent steps in testosterone production: AKR1C3 and 17BHSD3.

For the study, the researchers examined soft-tissue prostate-cancer metastases obtained from eight medically or surgically castrated men via the University of Washington rapid-autopsy program, one of a handful of such programs in the nation. For control purposes, the researchers also examined benign and cancerous prostate tissue from eight men who underwent radical prostatectomy for early-stage, localized prostate cancer, and prostate tissue from two men whose prostates were removed for reasons unrelated to prostate cancer.

The researchers also examined metastatic human prostate-cancer cells, obtained from androgen-deprived men, which had been engrafted and allowed to grow in both castrated and non-castrated mice, a process called xenografting.

Androgen levels in the xenograft tumors in the castrated mice, which had no circulating androgen, were actually higher than in the xenograft tumors in the mice that had not been castrated. The researchers found a particularly striking difference in levels of DHT. "We found DHT levels to be twice as high in the castrated mice," Mostaghel said. "That tells us that the tumor is making testosterone and hanging on to it somehow and is further evidence that metastatic tissue has the capacity to make its own testosterone."

Each year, approximately 200,000 U.S. men are diagnosed with prostate cancer. While the majority of cases are early-stage, localized disease -- due in large part to the widespread use of PSA, or prostate-specific antigen screening -- an estimated 50 percent of patients diagnosed and treated for clinically localized prostate cancer will progress to more advanced disease, which kills an estimated 30,000 American men annually.

Funding sources for this research included the National Institutes of Health, the Department of Defense and the Prostate Cancer Foundation.

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SOURCE Fred Hutchinson Cancer Research Center
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