Cleveland Clinic receives grant to study role of DNA damage in treatment-resistant prostate cancer

Wednesday, December 18, 2013: Cleveland Clinic, along with the National Cancer Institute, the University of Chicago and Thomas Jefferson University, are the recipients of a $600,000 Special Challenge Award from the Prostate Cancer Foundation (PCF) to investigate the role of abnormally high protein levels in prostate tumors.

The increased expression of approximately 25 proteins – referred to as interferon-related DNA damage resistance signature (IRDS) – correlates strongly with resistance to radiation and chemotherapy. African-American men with prostate cancer are much more likely to have the IRDS signature than Caucasian men, one potential reason for the observed differences in mortality from the disease.

"African-American men have a two-fold higher mortality rate from prostate cancer than European-Americans," said Eric Klein, M.D., Chairman, Glickman Urological & Kidney Institute at Cleveland Clinic, and principal investigator on the grant. "The goal of our research is to further investigate the biology behind the obvious aggressive behavior of prostate tumors in African-American men in the hopes of better understanding its biology and identifying new management and treatment options."

Cleveland Clinic is at the forefront of identifying and addressing health disparities through multidisciplinary clinical care, community outreach and education. In 2003, the Minority Men's Health Center, led by urologist Charles S. Modlin, M.D., MBA, was established in the Glickman Urological & Kidney Institute to address the vast number of medical conditions which disproportionately affect minority men. Approximately 750 patients visited the center this year, in addition to the more than 1,000 men who attend the annual Minority Men's Health Fair each April.

Prostate cancer tumors develop IRDS when exposed to interferons, potent antiviral proteins naturally produced by the body in response to a virus, bacteria or tumor cells. Inteferons were previously thought to prevent tumors from growing; however, research has shown their presence in certain tumors actually inhibits the effectiveness of traditional chemotherapy or radiation. Why this happens more frequently in African-American men is still unknown.

"We don't know whether the tumors themselves or tumor-associated immune cells are the primary sources of the interferon which enables the cancer cells to resist therapy or how such resistance is achieved," said George Stark, Ph.D., staff researcher in molecular genetics in Cleveland Clinic's Lerner Research Institute and principal investigator on the grant. "These questions are being actively investigated in our laboratories."

Part of the study will involve testing drugs conventionally used to treat other cancers to determine if they will block the growth response of prostate tumors when exposed to interferons, improving the tumor's response to chemotherapy or radiation and increasing survival rates. The grant – provided by PCF, a philanthropic organization that seeks to fund and accelerate prostate cancer research globally – will be also used to study a wide range of other clinical issues in IRDS-positive tumors.

"Overall, we hope our research will provide patients with IRDS-positive tumors a therapeutic approach that improves outcomes," said Dr. Klein.

Other Cleveland Clinic investigators involved in this research project include Andrew Stephenson, M.D. and Robert Silverman, Ph.D.

Provided by Cleveland Clinic