UF Health Cancer Center researchers have found that two DNA-damaging compounds may be able to overcome resistance to drugs commonly used to treat patients with advanced-stage prostate cancer.
This combination could potentially make up a new treatment approach for patients with this disease, according to the study, published recently in the Nature journal Cell Death & Disease and led by Alexander Ishov, Ph.D., an associate professor in the Department of Anatomy and Cell Biology in the UF College of Medicine and member of the UF Health Cancer Center.
Prostate cancer is the second leading cause of cancer-related death in American men. When prostate cancer recurs or progresses after hormonal therapies, it often spreads to other areas of the body which is a major cause of death for these men. There are few available treatments when this spread occurs, and those therapies that are available often have limited success because the cancer develops resistance.
One reason for this drug resistance is an increase in a protein called ABCB1 in prostate cancer cells. This protein is an attractive target for drugs development, yet ABCB1 inhibitors lack specificity and cause toxicity, limiting their clinical use.
“As the result, it is important to look for new strategies to overcome cancer drug resistance,” Ishov said.
In the new study, the team set out to study resistance to two drugs (from a category of chemotherapy called taxanes) commonly used in patients with prostate cancer: docetaxel and cabazitaxel. The team did these tests in prostate cancer cell cultures and 3D models.
They found that two different DNA-damaging compounds, camptothecin and cytarabine, were able to kill taxane-resistant cells despite high ABCB1 levels. The team further found that a targeted therapy (a small-molecule CDK4/6 inhibitor) further enhanced the effect of these compounds in overcoming drug resistance.
The findings indicate that the two DNA-damaging compounds, either on their own or in combination with the targeted CDK4/6 inhibitors, might form a new treatment regimen for patients with relapsed or unresponsive prostate cancer, the researchers said.
In addition to Ishov, co-authors from the UF Health Cancer Center’s Mechanisms of Oncogenesis research program were Olga Guryanova, M.D., Ph.D., Bowen Yan, Ph.D., Jason Brant, Ph.D., and Rene Opavsky, Ph.D.
Funding for the new study came from the National Cancer Institute, the National Institutes of Health, and a pilot grant from the UF Health Cancer Center, which receives crucial support for its research from the Casey DeSantis Cancer Research Act (Fla. Stat. § 381.915).
In addition to this research, the UF Health Cancer Center engages in a variety of community activities to help educate the public on cancer screening to reduce the risk of developing advanced disease, such as its Power Over Cancer series. In the expansive North and Central Florida region that the UF Health Cancer Center serves, there are higher mortality rates for prostate cancer in the Black population than the white population. Screening and early detection are key to help improve outcomes for all men.
Read the study in Cell Death & Disease.
For more information on prostate cancer clinical services, including screening at UF Health, resources, or clinical trials, visit https://ufhealth.org/conditions-and-treatments/prostate-cancer.
