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The Patrick C. Walsh Prostate Cancer Research Fund
A New Way to Track Prostate Cancer’s Response to Treatment
Is the treatment killing the cancer? This is a question that Theodore L. DeWeese, M.D., Director of Radiation Oncology and Molecular Radiation Science, oncologist Srinivasan Yegnasubramanian, M.D., Ph.D., and postdoctoral fellow Omar Mian would really like to be able to answer in as little time as possible, because with high-risk prostate cancer, the stakes are high.
This year, nearly 30,000 American men are estimated to die of prostate cancer, says DeWeese, the Peter Jay Sharp Foundation Scholar. “Many of these men were initially diagnosed with aggressive, or high-risk prostate cancer,” perhaps with disease that extended beyond the prostate, or had a high Gleason score, or a PSA level greater than 20 ng/ml. “Nearly half of these men will have a recurrence of their cancer after treatment.” A mainstay of care for men with highrisk prostate cancer is a combination of radiation and androgen deprivation therapy (ADT), DeWeese says, and “one of the challenges is the lack of a r eliable test allowing clinicians to monitor tumor response, both during and after radiation therapy.” The most commonly used marker, PSA, is not as useful in men receiving ADT, he adds, because “the PSA level is strongly suppressed by the ADT and is a less r eliable surrogate for detecting active tumor.” Because these men receive ADT during the radiation and for up to thr ee years afterward, “this limits the usefulness of PSA testing for an extended period of time, during which the window for curative therapies may close.” What’s needed, the scientists believe, is an “accurate, noninvasive monitoring test to guide early implementation of salvage strategies aimed at increasing the proportion of patients cured of their disease.”
Research done by their group and others has shown that prostate cancers “nearly universally harbor stable, cancerspecific changes of the DNA. This modified DNA can be detected in urine and blood specimens,” says DeWeese. “We hypothesize that genome-wide assessment of these cancer-specific DNA changes in the blood and urine of prostate cancer patients, using technology developed by our group, called qMBD-seq, will allow for more helpful and accurate tracking of the cancer and the response to therapy in these high-risk men receiving radiation therapy and ADT.”
In an early-phase clinical study, DeWeese, Yegnasubramanian, and Mian are establishing the background levels of modified DNA in the urine and blood of men with no history of prostate cancer. “Then, we will quantify cancer-specific DNA abnormalities in the urine and blood of men known to have high-risk prostate cancer at multiple time points before, during, and after radiation treatment. These samples will be analyzed using our genome-wide qMBD-seq approach, allowing us to simultaneously characterize and quantify prostate cancer-specific DNA. This will allow us to predict which men have prostate cancer still present in their body after treatment, even if their PSA is very low or even undetectable.”