Medical College of Wisconsin researchers discover potential new treatment for prostate cancer

Milwaukee, March 9, 2018 – Radiation therapy long has been one of the key treatment options for localized prostate cancer, the most common non-skin cancer among U.S. men.

For more than a decade, Medical College of Wisconsin researchers have been at the forefront of the evolution of adaptive radiation therapy with the goal of providing more personalized treatments. Marja T. Nevalainen, MD, PhD. Dr. Nevalainen, Director of Prostate Cancer Center of Excellence at the Medical College of Wisconsin (MCW) Cancer Center, and a team of MCW and national researchers have uncovered a novel approach that may more effectively treat prostate cancer and reduce side effects.

The researchers found that expression of the protein Stat5 in prostate cancer controls the expression of a set of genes that promotes DNA repair, according to Nevalainen, an internationally recognized researcher on prostate cancer. Because radiation therapy is effective in prostate cancer by causing DNA damage, Stat5 expression in prostate cancer makes the radiation therapy less effective. Dr. Nevalainen had previously developed a new drug to inhibit Stat5, and the use of this Stat5 inhibitor with radiation therapy in human prostate xenograft tumors in mice greatly enhanced the effects of the radiation. Importantly, the Stat5 inhibitor did not make normal tissues more sensitive to radiation. These studies demonstrate that Stat5 inhibition can be used as a treatment strategy to enhance the beneficial effects of radiation therapy. Essentially, Stat5 inhibition can sensitize prostate cancer cells to radiation and potentially allow doctors to lower the doses of radiation used to kill the tumor cells, Dr. Nevalainen explained.

"Improving the efficacy of radiation therapy while reducing side effects could improve the quality of life of prostate cancer patients when they go through their treatments in the future," Nevalainen said.

Findings from the National Cancer Institute funded research project entitled, "Stat5a/b Blockade Sensitizes Prostate Cancer to Radiation through Inhibition of RAD51 and DNA Repair," have been published in the American Associate of Cancer Research (AACR) journal Clinical Cancer Research. The novel findings of this study could eventually result in major changes to the way medical professionals treat prostate cancer, which is diagnosed in 1 in 7 men in the U.S. during their lifetime.

"Improving the efficacy of radiation therapy may reduce the likelihood of prostate cancer recurrence, ultimately also leading to less prostate cancer metastasis and prostate cancer deaths," Nevalainen said.

The paper can be found on the Clinical Cancer Research website.

The Prostate Cancer Center of Excellence at MCW Cancer Center is a multi-disciplinary hub for prostate cancer research within the college that also facilitates collaboration with an international network of prostate cancer researchers. A team of MCW and national researchers was formed to participate in this research project. The team includes MCW researchers Cristina Maranto, PhD, Vindhya Udhane, PhD, Kareem Malas, PhD, Karmel Cardenas, Ken A Iczkowski, PhD, and Sara M. Schmitt of the Department of Pathology, Prostate Cancer Center of Excellence at MCW Cancer Center, Carmen Bergom, MD, PhD, Department of Radiation Oncology at MCW, and Ken Jacobsohn, MD, and William See, MD, of the Department of Urology, Prostate Cancer Center of Excellence at MCW. East Coast-based researchers David T. Hoang, PhD, and Lei Gu, PhD, of the Department of Cancer Biology, Kimmel Cancer Center at Thomas Jefferson University, Vitali Alexeev, PhD, and Ulrich Rodeck, PhD, of the Department of Dermatology, Thomas Jefferson University Medical College, and Jonathan R Brody, Department of Surgery, Sidney Kimmel Cancer Center, Thomas Jefferson University also participated in this research project.

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