A Cleveland Clinic-led research team discovered how tumors evade prostate cancer therapy and identified a short timespan in which hard-to-treat tumors may respond to treatment, opening the door—or window—to potential new strategies.
While antiandrogen therapy is a key aspect of advanced prostate cancer treatment, patients can develop a resistance to the drugs. Researchers at Cleveland Clinic, in collaboration with U.K.-based Institute of Cancer Research and Canada-based Princess Margaret Cancer Center, used genetic and chemical signaling to identify underlying mechanisms of drug resistance after standard antiandrogen therapy. Their findings were published May 18 in Proceedings of the National Academy of Sciences.
The team found that a highly complex tumor response occurs during prostate cancer drug resistance. Part of the response to hormonal therapy includes a window of time in which tumors briefly express “virus-like” elements and trigger an immune signaling in the tumor that may make them respond 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, M.D., lead study author and director of the Genitourinary Malignancies Research Center at Cleveland Clinic’s Lerner Research Institute and the Kendrick Family Endowed Chair for Prostate Cancer Research. “More research is needed but this could be a promising strategy for overcoming this drug resistance and immune evasion in prostate cancer.”
The findings build off research published last spring, also from Sharifi and the Cleveland Clinic team, showing that inhibiting the protein H6PD in prostate tumors restored their responses to standard treatments. The most recent research 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.
A separate potential prostate cancer treatment in the works is one that exploits an RNA molecule with the power to tamp down prostate tumors. Researchers at Washington University School of Medicine in St. Louis discovered a long noncoding RNA that regulates the androgen receptor. Suppressing the androgen receptor dialed up expression of the RNA in mouse models of prostate cancer, causing tumors to shrink, they reported in the journal Cancer Research.