Uncovering the Mysteries of Prostate Cancer
Prostate cancer research at the University of Wisconsin-Madison 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.
Research in Prostate Tumor Development and Treatment
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.
Studying the Sonic Hedgehog Gene
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. In 2009, 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.
Androgen Independent Prostate Cancer
Androgen independent prostate cancer is thought to arise from a small fraction of tumor cells with features of tissue-specific stem cells. The study of tumor stem cells and tissue-specific stem cells has been hampered by lack of an effective method to isolate, identify and characterize cells with stem cell properties.
Dr. Wade Bushman is hypothesizing that anchorage independent culture maintains a population of pleuripotent prostate stem cells. He is culturing freshly isolated prostate epithelial cells in anchorage-independent "prostaspheres" and characterizing the ability of cells maintained in anchorage-independent culture to exhibit stem cell properties in a tissue recombination assay.