A treatment paradox has recently come to light in prostate cancer: blocking testosterone production halts tumor growth in early disease, while elevating the hormone can delay disease progression in patients whose disease has advanced.
Pharmaceutical suppression of male hormones has long been a lifesaver, but in more advanced cases, raising levels has profound clinical benefit The inability to understand how different levels of the same hormone can drive different effects in prostate tumors has been an impediment to the development of new therapeutics that exploit this biology.
"For decades, the goal of endocrine therapy in prostate cancer has been to achieve absolute inhibition of androgen receptor function, the protein that senses testosterone levels," said lead investigator Rachid Safi, Ph.D., research assistant professor in the Department of Pharmacology and Cancer Biology, at Duke University School of Medicine.
It turned out to be rather simple. When androgen levels are low, the androgen receptor is encouraged to"go solo" in the cell. In doing so, it activates the pathways that cause cancer cells to grow and spread. However, as androgens rise, the androgen receptors are forced to"hang out as a couple," creating a form of the receptor that halts tumor growth.
"Our study describes how BAT and like approaches work and could help physicians select patients who are most likely to respond to this intervention," McDonnell said."We have already developed new drugs that exploit this new mechanism and are bringing these to the clinic for evaluation as prostate cancer therapeutics."Rachid Safi, Suzanne E. Wardell, Paige Watkinson, Xiaodi Qin, Marissa Lee, Sunghee Park, Taylor Krebs, Emma L.
Men's Health Prostate Health Urology Cancer Diseases And Conditions Colon Cancer Lung Cancer
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