V Foundation Funds Sylvester-Led Strategy to Break Pancreatic Cancer Resistance
Summary
- A new study published in JCI Insight identifies IL1RAP as an important driver of pancreatic cancer resistance and a promising therapeutic target.
- A competitive V Foundation grant to Dr. Jashodeep Datta supports the scientific study.
- These discoveries are advancing into a first-of-its-kind pancreatic cancer clinical trial at Sylvester.
Pancreatic cancer remains one of the most difficult cancers to treat. A key reason is its tumor microenvironment, a complex network of cells that helps tumors resist chemotherapy and immunotherapy.
Although recent headlines highlight a new KRAS-targeted therapy that extends survival in patients with metastatic cancer, this paradigm will take years to extend to patients with operable pancreatic cancer. The need for new strategies in the latter population is urgent and ongoing.
According to the American Cancer Society, pancreatic cancer accounts for a relatively small percentage of new cancer diagnoses each year. Still, it remains one of the leading causes of cancer-related deaths.
At Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, researchers are working to change that trajectory.
For years, Jashodeep Datta, M.D., pancreatic and hepatobiliary surgical oncologist, co-leader of the Gastrointestinal Site Disease Group at Sylvester and assistant director of transdisciplinary research at Sylvester, has studied how the tumor microenvironment and the immune system shape cancer growth and treatment resistance.
“My work is driven by the bedside-to-bench-to-bedside arc, taking the most urgent questions my patients face, dissecting them at a granular level in the lab and translating the insights into new therapies that meaningfully improve both quality and length of life,” said Dr. Datta, the DiMare Family Endowed Chair in Immunotherapy and associate professor in the Division of Surgical Oncology at the Miller School.
Decoding a Resistant Microenvironment
At the center of this work is IL1RAP, a receptor that sits at a key control point in inflammatory signaling. In a new study published in JCI Insight, Dr. Datta’s team shows how IL1RAP connects tumor cells, immune cells and fibroblasts into a coordinated network that sustains cancer’s resistance to treatment. Instead of acting alone, pancreatic tumors rely on surrounding cells to survive and adapt.
“When we target IL1RAP, we are blocking a shared ‘helper’ receptor that many inflammatory signals rely on to transmit their message,” said Dr. Datta.
By blocking that bottleneck, researchers can dampen an entire network of tumor-driven inflammation. That is critical in pancreatic cancer because this “inflamed but immune-suppressed” environment is a major reason chemotherapy and immunotherapy often fall short. Elevated IL1RAP helps tumors sustain their growth and treatment resistance.
Turning Insight into Intervention
If IL1RAP helps tumors maintain their defenses, then blocking it may help break them down. The Sylvester team found in preclinical research that inhibiting IL1RAP reshapes the tumor microenvironment. Immune-suppressive cells decrease while T cells become more active and effective. Tumors show less fibrosis and an improved response to combination therapy.
The goal is not just to attack cancer cells, but to reprogram the environment that protects them, making existing treatments work better, explained Dr. Datta.
By identifying IL1RAP as a therapeutic vulnerability and linking its activity to treatment response, the early-stage results lay the groundwork for a new strategy to confirm this link. Based on these findings, a neoadjuvant clinical trial in patients is now advancing at Sylvester, combining IL1RAP-targeted therapy with chemoimmunotherapy in patients with operable pancreatic cancers prior to surgery.
“Moving this work into a clinical trial is a landmark development for our GI cancer program at Sylvester,” Dr. Datta said. “We’re testing a clear, patient-centered strategy to disrupt IL1RAP using a treatment plan that can be delivered in the clinic.”
V Foundation Grant
The trial allows researchers to evaluate tumors before and after treatment, offering a rare opportunity to understand how a patient’s biology changes.
“Every new approach helps us learn more,” said Peter Hosein, M.D., co-author of the study, co-leader of the Gastrointestinal Cancers Site Disease Group at Sylvester, associate director for clinical research at Sylvester Pancreatic Cancer Research Institute and professor of medical oncology at the Miller School. “This trial gives us a unique window to connect the science directly to patient outcomes, which is essential for moving the field forward.”
The work is supported by a competitive translational research grant from the V Foundation to Dr. Datta and his research team, placing it among a small cohort of funded translational teams selected each year. The nominees for this grant undergo national peer review before selection. Those selected receive $800,000 over four years to support their “bench-to-bedside” research and to advance novel strategies into early-phase clinical trials.
“It is a strong endorsement that our science at Sylvester is rigorous, world-class and positioned to move meaningful biology toward clinical impact,” Dr. Datta said.
Elevating the Next Generation
Trainees played a central role in the research, contributing to experiments and data analysis while gaining experience across the full spectrum of translational science.
“Involving the next generation is essential because projects like this teach the full life cycle of translational cancer research, from discovery to mechanism to biomarkers to clinical trial design, and prepare trainees to become the future leaders who will carry this work forward for patients,” Dr. Datta said.
His team included:
• Co-first author Maggie Marsh, a graduate student who led key experiments and data analysis
• Co-first author Erin Dickey, M.D., a former T32 Surgical Oncology research fellow and current general surgery resident who helped drive preclinical experiments with the study drug;
• Anna Bianchi, Ph.D., principal scientist in the Datta Lab who oversees research operations.
A New Chapter in Pancreatic Cancer Research
Pancreatic cancer remains one of the most difficult malignancies to treat. But research like this suggests its defenses may not be permanent. The true impact on patient survival will depend on the outcomes of the upcoming trial.
By targeting IL1RAP and disrupting the communication networks that sustain resistance, researchers may uncover a new way to make tumors vulnerable again. This reflects a shift in strategy, from attacking the tumor directly to reshaping the environment that sustains it.
In many ways, it is like altering the climate rather than the storm itself. And for patients, that shift could mark the beginning of a new chapter, one defined not by resistance, but by response.
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Tags: cancer research, chemotherapy, Dr. Jashodeep Datta, Dr. Peter Hosein, immune system, immunotherapy, Newsroom, pancreatic cancer, Sylvester Comprehensive Cancer Center