Scientists Find a Way to Weaken Pancreatic Cancer's Protective Shield

Researchers at the Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, have identified a way to weaken one of pancreatic cancer's key defenses against treatment by blocking a receptor called IL1RAP, which helps coordinate the network of cells surrounding pancreatic tumors. The work, published in the journal JCI Insight, is now moving toward a clinical trial.

Pancreatic cancer remains among the hardest cancers to treat, largely because of the tumor microenvironment — the community of cells and tissue surrounding a tumor that helps it survive and resist therapy. Led by Dr. Jashodeep Datta, the researchers found that IL1RAP acts as a shared "helper" receptor that many inflammatory signals rely on, linking tumor cells, immune cells and fibroblasts into a system that supports resistance to treatment.

In preclinical studies, blocking IL1RAP changed the tumor microenvironment in several ways: immune-suppressive cells became less abundant, T cells (immune cells that can attack tumors) became more active, and tumors developed less fibrosis and responded more strongly to combination treatment.

Based on these findings, Sylvester is now advancing a neoadjuvant clinical trial — meaning treatment given before surgery — that will combine IL1RAP-targeted therapy with chemoimmunotherapy in patients with operable pancreatic cancer. Because patients will receive treatment before surgery, researchers will be able to examine tumors both before and after therapy.

The research is supported by a Translational Research Grant from the V Foundation, which is providing $800,000 over four years to help move the strategy from the laboratory into early-phase clinical trials.