Ramesh Narayanan, PhD, professor in the Department of Medicine and the Division of Hematology and Oncology at the University of Tennessee Health Science Center, has received a $455,000 grant from the National Cancer Institute for a two-year study of the underlying cause of the development of aggressive prostate cancer in African American men.
Approximately 174,000 men in the United States were diagnosed with prostate cancer and 31,000 died of the disease in 2019. The number of men with prostate cancer is expected to increase from 3.3 million men currently to 4.5 million by 2026.
Current therapeutic strategies target androgen (hormone) activity for aggressive, or advanced castration-resistant prostate cancer. Although these drugs on average extend progression-free survival, approximately 30 percent of tumors do not respond to these therapies, and patients who initially respond to these therapies develop resistance shortly after treatment initiation.
One of the primary reasons for treatment failure and relapse is the expression of a shortened form of the receptor protein for androgens (AR). These different versions are called AR splice variants (AR-SVs). Prostate cancers that express this shortened form are aggressive and fail to respond to current treatments.
Compared to Caucasian men, African American men have a 63 percent higher overall prostate cancer incidence. These individuals are more likely to be diagnosed with aggressive and potentially lethal cancers, are more than twice as likely to die from prostate cancer, and have shorter disease-free survival.
Inadequate health care that limits early cancer detection or results in incomplete treatment could factor into the diagnosis of advanced cancer and a worse prognosis in African American men compared to Caucasian men. However, a prior analysis of men undergoing prostate biopsy that adjusted for clinical and demographic differences found that African American men were 50 percent more likely to be diagnosed with prostate cancer and 84 percent more likely to have high-grade cancer than Caucasian men.
Considering that approximately 65 percent of the population in the Memphis area is African American, it is appropriate and locally relevant to evaluate the underlying mechanisms for the aggressive prostate cancer development in African American men.
This grant will ask the question whether prostate cancers in African American men have higher expression of the shortened form of the AR (AR-SVs) and whether these AR-SVs are the primary mediator of the aggressive cancer. If the data proves the hypothesis that the higher expression of AR-SVs in prostate cancer of African American results in aggressive disease, Dr. Narayanan’s laboratory has developed novel drugs that have the potential to target the AR-SVs and inhibit the aggressive prostate cancer.
The multi-disciplinary UTHSC team that will work on this project includes Jay Fowke, PhD, MPH, MS, chief of Division of Epidemiology and professor in the Department of Preventive Medicine; Mahul Amin, MD, chair of the Department of Pathology; Robert Wake, MD, professor and chair of the Department of Urology; and Maurizio Buscarini, MD, PhD, MBA, professor of the Department of Urology.
“I have been working for the last seven years at UTHSC to discover next-generation drugs to treat advanced aggressive prostate cancer,” Dr Narayanan said. “This work in collaboration with Dr. Duane Miller (Professor Emeritus in the Department of Pharmaceutical Sciences at UTHSC) has resulted in novel molecules that are advancing toward clinical trials. If our results show that African American men express the shortened AR protein AR-SV at higher levels, our drugs will provide hope to these patients, who currently do not have alternate treatment options. It will be gratifying to see our research benefit the Memphis community and the prostate cancer patient population across the world.”