Can Gut-Protective Therapy Make Pancreatic Cancer Treatment Better?
Article Summary
- Chemotherapy-induced gastrointestinal toxicity and systemic inflammation are two key obstacles to effective treatment of pancreatic cancer.
- Dr. Nagaraj Nagathihalli will study whether urolithin A can protect the gut and reduce systemic inflammation.
- The research is designed to align with real-world therapeutic challenges and quickly translate into clinical interventions.
Pancreatic cancer is one of the toughest cancers to treat because it grows so aggressively and many patients cannot tolerate the harsh chemotherapy needed to fight it.
With a Florida Cancer Innovation Fund grant worth approximately $1.5 million, researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, are exploring a compound, urolithin A (UroA), which may protect the gut and reduce inflammation. If it works, it could make powerful treatments easier to tolerate and bring hope for more effective, life-saving care.
Nagaraj Nagathihalli, Ph.D., assistant director of the Pancreatic Cancer Research Institute at Sylvester, is leading the study. His work will specifically focus on pancreatic ductal adenocarcinoma, which accounts for 90% of pancreatic cancer diagnoses.
“Pancreatic cancer remains one of the deadliest malignancies and has limited treatment success, partly due to the systemic toxicity of chemotherapy,” said Dr. Nagathihalli, also an associate professor in the DeWitt Daughtry Family Department of Surgery. “Our approach seeks to strengthen the gut barrier and reduce inflammation — two key obstacles limiting therapy effectiveness — by leveraging a natural gut-microbiome metabolite known as urolithin A.”
Dr. Nagathihalli’s project builds on a growing body of work emphasizing the gut-tumor axis. His research group is at the forefront of host-directed cancer therapy. This rapidly emerging approach that targets nonmalignant systems in the patient’s body to optimize oncologic outcomes.
This project is primarily focused on high-risk populations, such as patients with a history of tobacco use. People in these groups often exhibit exacerbated treatment-related toxicity and poor therapeutic tolerance when receiving chemotherapy.
Innovation at the Intersection of Microbiome Science and Cancer Therapy
To see how UroA might help protect the gut during chemotherapy, Dr. Nagathihalli’s team will create models that mimic the damage chemo can cause. Some of the models represent people who smoke, some those who don’t. This is a key part of the study because smoking can make gut problems worse. By comparing these models, researchers hope to learn whether UroA can close the survival gap between these two groups and restore a healthy balance of gut bacteria.
A compound like urolithin A, which may protect the gut and reduce systemic inflammation, could be a major advance. It represents a shift toward supportive therapies that make curative treatment more accessible and effective.
Dr. Peter Hosein
They’ll also test whether UroA can protect against damage from common chemo drugs like gemcitabine, paclitaxel and FOLFIRINOX, and figure out exactly how UroA works at the molecular level. Dr. Nagathihalli’s research will test UroA’s ability to:
• Preserve the overall health and function of the gut lining
• Regulate tight junction proteins that serve as the physical barrier between gut cells and help maintain a sealed and selective gut lining
• Curb systemic inflammation
• Impact inflammatory signaling, immune response and gene regulation
This project will also examine how changes in gut microbial diversity alter responses to therapy. The team will study stool samples in two ways. First, they’ll zoom in to examine individual cells’ gene activity. Then, they’ll zoom out to look at the bigger picture by examining all the genetic material from the microbes living in the sample.
In the second phase, the study will track long-term results of UroA-enhanced chemotherapy. The goal is to observe if this treatment can slow cancer growth while causing as little harm as possible.
If successful, these findings could help lay the groundwork for the first human clinical trials.
Translating Lab Science Into Better Outcomes for Pancreatic Cancer Patients
Peter Hosein, M.D., a medical oncologist who is one of the principal investigators in this study and co-leader of Sylvester’s Gastrointestinal Cancers Site Disease Group, emphasized the urgency of translating this research for clinical use.
“One of the greatest challenges we face in treating pancreatic cancer is not just the aggressiveness of the disease, but the inability of patients to tolerate the full intensity of chemotherapy,” explained Dr. Hosein, also associate director for clinical research at Sylvester Pancreatic Cancer Research Institute and professor in the Division of Medical Oncology at the Miller School. “This is especially true for patients who are already medically vulnerable due to smoking or other comorbidities. A compound like urolithin A, which may protect the gut and reduce systemic inflammation, could be a major advance. It represents a shift toward supportive therapies that make curative treatment more accessible and effective.”
Dr. Hosein’s clinical insights are helping shape the project to translate laboratory research into clinical interventions quickly. He ensures that the project’s experiments are designed to align with real-world therapeutic challenges, which will be particularly important as the team works toward developing clinical trials.
While centered on pancreatic ductal adenocarcinoma, the study’s implications extend to other cancers where chemotherapy-induced GI toxicity, inflammation and microbiome disruption may limit therapeutic benefit.
“This project underscores the importance of integrative strategies that combine molecular oncology, host biology and microbiome science,” Dr. Nagathihalli said. “Our long-term goal is to reframe how we approach treatment side effects — not as inevitable consequences, but as modifiable barriers to success.”
Tags: chemotherapy, Dr. Nagaraj Nagathihalli, Dr. Peter Hosein, Gastrointestinal Cancers Site Disease Group, pancreatic cancer, Sylvester Comprehensive Cancer Center, USNWR Oncology 2026