Sylvester researcher, Nagaraj Nagathihalli, Ph.D., is testing an innovative strategy against pancreatic cancer using a combination of synthesized natural compounds and immunotherapy.

“There is a desperate need to develop novel therapeutic approaches in pancreatic cancer that reduce tumor burden and improve overall survival without producing significant off-target effects,” said Dr. Nagathihalli, assistant professor of surgery at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. “If successful, this combination will provide a rationale to scale up to clinical studies.”

Dr. Nagathihalli received a two-year R03 grant for $76,750 from the National Cancer Institute for a project titled “Combining Immunotherapy with Urolithin A to Improve Pancreatic Cancer Survival.” Urolithin A is a natural compound derived from pomegranates that has potent antitumor effects. The new NCI-funded study builds on Dr. Nagathihalli’s pre-clinical research showing that a microbial metabolite, Urolithin A, derived from a compound found in berries and pomegranates, can reduce and protect against pancreatic cancer in a laboratory model.

In that study, Dr. Nagathihalli and his team showed that Urolithin A can block tumor cell growth and improve survival in mouse models of pancreatic cancer. Interestingly, Urolithin A treatment also induced dramatic changes to the immune cell composition within tumors, suggesting that it could enhance the ability of the host immune system to fight pancreatic cancer.

“Pancreatic cancers are notorious for their ability to evade detection by the body’s immune system. Our preclinical data demonstrate that Urolithin A can alter the immunologically ‘cold’ pancreatic cancer microenvironment and result in a high accumulation of reactive T cells that could indicate synergism with immunomodulatory therapies,” said Dr. Nagathihalli. 

“We are investigating how we can combine checkpoint inhibitors – which enhance the ability of T cells to kill the cancer cells – with Urolithin A treatment to improve survival in experimental models,” he added.