Posted: Monday, January 9, 2023
Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine may have unlocked the potential of nitric oxide in the treatment of castration-resistant prostate cancer. Their preclinical study findings, which were presented in the journal Nature Cell Death & Disease, suggest that reducing oxidative stress with exogenous nitric oxide may sensitize tumors to a therapy that blocks the CSF1 receptor, thereby rebalancing the immune components in the tumor microenvironment.
“By doing this, we can reduce the burden of these highly resistant tumors,” said study author Himanshu Arora, PhD, in an institutional press release. “We can combine immunotherapies with nitric oxide to make them more effective. We hope to begin preliminary, phase I clinical trials to test these therapies in combination and hopefully improve patient outcomes.”
The researchers focused specifically on aiming to block the CSF1 receptor with the administration of nitric oxide, which “could act as an effective combinatorial partner with CSF1R blockade against castration-resistant prostate cancer,” they added. Studies have failed to block CSF1 thus far, and the team proposed several reasons why. They were able to determine that the enzyme nitric oxidize synthase 3 stops producing nitric oxide, preventing the CSF1 receptor from being nitrosylated, resulting in an imbalance between macrophages in the tumor microenvironment. As a result of this, the tumor can better resist CSF1 inhibition.
The researchers discovered that they could support CSF1 nitrosylation by infusing nitric oxide, therefore improving CSF1 inhibition and shrinking prostate tumors. However, much more research is needed, and Dr. Arora and his colleagues plan on studying how nitrosylation and arginylation impact immune resistance in high-grade prostate cancers, as well as how these mechanisms may influence other immunotherapies, such as PD-L1 checkpoint inhibitors.
Disclosure: For full disclosures of the study authors, visit nature.com.