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Johns Hopkins

Johns Hopkins Pediatric

Breaking DNA and Killing Cancer

January 01, 2017

Some men who are treated for localized prostate cancer with radiation therapy also receive androgen deprivation therapy (ADT), or hormonal therapy. “Multiple studies have shown the striking benefits of reducing testosterone before and during a course of radiation therapy for men with Gleason 7-10 cancers, or those who have cancer that can be felt outside the prostate (stage T3),” says Theodore DeWeese, M.D., Chairman of the Department of Radiation Oncology and Molecular Radiation Science. “This has resulted in better control of cancer in the prostate, a decreased risk of cancer spreading, and an improvement in survival.

In the laboratory, Hopkins scientists have found that depriving human prostate cancer cells and tumors of testosterone and then briefly replacing high-dose testosterone causes a large number of breaks in the DNA. This is good: if not repaired, DNA breaks can lead to cell death. “Radiation also leads to large amounts of DNA breaks in cancer cells, resulting in cell death,” says DeWeese. In work with Vasan Yegnasubramanian, M.D., Ph.D., DeWeese has found that “when testosterone and other drugs that bind to the androgen receptor of prostate cancer cells are combined with radiation, even greater number of DNA breaks occur, resulting in much greater tumor control.” These results are so promising that with postdoctoral fellow Jonathan Coulter, DeWeese and Yegnasubramanian are seeking the optimal combination of radiation and androgen receptor-binding drugs, “so that we can begin to test this in clinical trials."

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