Prostate cancer research at the UW Department of Urology is proceeding at a robust pace. This involves members of the department as well as a broad assortment of investigators across campus.
Dr. David Jarrard’s laboratory has been making important contributions in the fields of tumor development and treatment. Prostate cancer is strongly associated with aging. Dr. Jarrard has shown that epigenetic changes—permanent changes in gene regulation—occur in the prostate as a direct function of aging and alter the activity of genes involved in cancer development. These studies presage dietary interventions to slow the development of these changes and reduce the risk of cancer.
In other work, Dr. Jarrard’s laboratory has been investigating the potential of chemical agents to induce senescence in prostate cancer cells. Prostate cancer is highly resistant to chemotherapeutic agents that “kill” tumor cells. Senescence is a cell survival state in which tumor cells persist but no longer proliferate. Dr. Jarrard’s laboratory is providing insights that will help develop drugs to induce senescence in prostate cancer cells. The hope is to “mothball” those tumors that cannot be eradicated—allowing men with these tumors to be free from tumor progression. These studies have been supported by the National Institute of Health, the Department of Defense Prostate Cancer Program and the Livesey Chair in Urologic Oncology.
Dr. Wade Bushman’s laboratory focuses on fundamental biological processes involved in prostate cancer development and progression. Over the past 10 years, Dr. Bushman’s laboratory has led the study of the gene Sonic Hedgehog in prostate growth regulation and prostate cancer. Inhibitors of the Hedgehog pathway have been developed by several pharmaceutical companies and the introduction of these for the treatment of advanced prostate cancer will occur in the near future. More recent work has focused on prostate stem cells with an interest in understanding the development of androgen-independent cancer. And most recently, Dr. Bushman’s laboratory has been investigating how prostatic inflammation—long suspected as an etiologic factor in development of prostate cancer—reactivates growth pathways normally only active during development. This may be a critical step in tumor development and a target for cancer prevention. These studies have been supported by the National Institute of Health, the Department of Defense Prostate Cancer Program, the Prostate Cancer Foundation and the Schnoes Chair in Urologic Research.
The efforts of Drs. Jarrard and Bushman are a cornerstone of the UW Prostate Cancer Program. This program is large and growing, currently involving a total of 45 investigators supported by $15 million in annual research funding, including 13 investigators who are leaders on nationally funded basic research grants or prostate cancer clinical trials.
The UW Department of Urology is committed to advancing the knowledge and ability to treat urologic cancers through ground-breaking research as well as clinical efforts.
Highlights of the department’s research efforts in renal cancer include the initial description and characterization of ice-ball temperatures generated by the treatment modality known as cryoablation. Researchers in the Department were also the first to provide convincing animal data demonstrating the equivalent utility of this treatment approach relative to nephrectomy which had been considered the “gold standard” treatment of localized renal malignancy at the time. In addition, the Department of Urology was the first to develop and publish a murine model for the study of human renal cryoablation using closedtip cryoprobes and argon gas. This model remains an invaluable tool for further investigations performed at a number of institutions.
Studies conducted in the laboratory by Dr. Sean Hedican, Associate Professor of Urology at the University of Wisconsin, later demonstrated an immune mediated survival advantage of both cryoablation and radiofrequency ablation in the treatment of advanced renal malignancy superior to nephrectomy using the Department’s murine model. This work has been recognized at two consecutive World Congress Meetings in Endourology by a panel of international experts as the “Best Overall” and “Best Scientific” paper presented at these meetings. Additional investigations into the treatment of renal cancer being conducted by the Department include characterization of the cytokine response to cryoablation, the development of a virus-mediated cytokine gene delivery system to use in conjunction with cryoablation and radiographic imaging of the ablation sites using a newly developed imaging radiotracer. UW Urology’s experimental observations are already being applied to the care of patients with advanced renal malignancies at this and other institutions.
Researchers in the department have also continued their nationally recognized pursuits in the realm of bladder cancer. These efforts include the study of bladder cancer chemoprevention, early events in carcinogenesis and biological markers of recurrence and progression. Studies include the in vitro assessment of the dietary agent genistein (a soy protein) and green tea catechins to determine their efficacy in the inhibition of bladder cancer cell growth.
UW Urology continues its commitment to improve the health of urologic cancer patients through vigorous and innovative research programs bringing the “bench to the bedside.”