Personalized combination treatment turns on an immunometabolic switch to effectively control an aggressive form of prostate cancer

Researchers at the University of Chicago Medicine Comprehensive Cancer Center established “proof-of-concept” for a new treatment approach that was able to effectively treat a mouse model of the most aggressive forms of prostate cancer. The treatment showed complete tumor control and long-lasting survival without side effects in a mouse model of advanced prostate cancer.

These findings, published online September 18, 2023 in Akash Patnaik, MD, PhD, MMSc, an internationally recognized expert in prostate cancer research and treatment who is the senior author of the publication. “Although this form of treatment has been shown to have significant anti-cancer responses in patients, the majority will become resistant to hormonal therapy, or castrate-resistant.”

Advanced prostate cancers that don’t respond to standard hormone-based therapy, chemotherapy or immunotherapy leave patients with very few options. Researchers are working to develop urgently needed treatments for these aggressive cancers, collectively known as metastatic castration-resistant prostate cancer (mCRPC).

Patnaik’s lab develops targeted strategies to improve the responsiveness of prostate cancer to immunotherapy. They discovered that the immune system often promotes cancer growth — instead of suppressing it — through recruitment of abnormal tumor-associated macrophages that express PD-1 (a checkpoint molecule that turns off an anti-cancer immune response) into the tumor microenvironment.

In a Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient aggressive-variant prostate cancer via macrophage phagocytosis,” was supported by funding from the Prostate Cancer Foundation Izzy Englander Challenge Award and the National Cancer Institute.

Additional authors include Kiranj Chaudagar, Hanna M. Hieromnimon, Anne Kelley, Brian Labadie, Jordan Shafran, Srikrishnan Rameshbabu, Catherine Drovetsky, Kaela Bynoe, Ani Solanki, Erica Markiewicz and Xiaobing Fan from Akash Patnaik’s team at the University of Chicago and collaborator Massimo Loda from Weill Cornell Medicine.