How advanced prostate cancer becomes resistant to androgen-deprivation therapy

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.

Note for media only: To arrange an interview with Mostaghel, please contact Dean Forbes, Hutchinson Center Media Relations, at (206) 667-2896 or . To obtain a copy of the paper, “Maintenance of intratumoral androgens in metastatic prostate cancer: A mechanism for castration-resistant tumor growth,” please contact journal press officer Jeremy Moore at .

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