Researchers uncover how tumors circumvent prostate cancer therapy, identify promising treatment strategy

A Cleveland Clinic-led research team uncovered how tumors circumvent prostate cancer therapy and identified a promising new strategy for treatment. Findings were published in Proceedings of the National Academy of Sciences (PNAS).

Antiandrogen strategies remain the backbone for advanced prostate cancer treatment, but drug resistance develops and tumors progress. Using genetic and chemical signaling approaches, the research team identified underlying mechanisms of drug resistance to discover a potential treatment target.

They found that as prostate cancer drug resistance occurs, there is a highly complex tumor response during which tumors briefly express “virus-like” repeat elements and trigger an immune stimulatory response.

The data suggests that there is a window of time after treatment with hormonal therapy in which the tumors express these “virus-like” elements, which then induce immune signaling in the tumor that may make them responsive to immunotherapies.

“This is significant as it may tell us how prostate cancers, which are known not to respond to immunotherapies, could then flip on responsiveness to these therapies,” said Nima Sharifi, MD, lead author of the study. “More research is needed but this could be a promising strategy for overcoming this drug resistance and immune evasion in prostate cancer.”

Dr. Sharifi is director of the Genitourinary Malignancies Research Center at Cleveland Clinic’s Lerner Research Institute and the Kendrick Family Endowed Chair for Prostate Cancer Research. Co-first authors are Drs. Mehdi Baratchian and Ritika Tiwari. Collaborating institutions include Royal Marsden Hospital in the U.K. and Princess Margaret Cancer Center in Toronto.

The work was supported by grants from the National Cancer Institute, the Prostate Cancer Foundation, the National Institute for Allergy and Infectious Disease, and the Department of Defense.