Study identifies IL1RAP as target to weaken pancreatic cancer's protective shield

Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine identified a receptor called IL1RAP as a signaling hub that links cancer cells, immune cells, and fibroblasts in the dense microenvironment surrounding pancreatic tumors. The study, published in JCI Insight, found that disrupting IL1RAP weakens the protective scar-like tissue that shields pancreatic tumors from treatment and limits drug penetration. Pancreatic tumors develop a dense, fibrous microenvironment that suppresses immune responses and helps cancer cells survive under stress. Even when chemotherapy damages cancer cells, the surrounding cellular network can help the disease recover and adapt. Recent advances with KRAS-targeted drugs have generated optimism for metastatic disease, but bringing similar progress to patients with operable pancreatic cancer may take years, underscoring the need for strategies testable in the preoperative setting. The researchers found that IL1RAP transmits multiple inflammatory signals and acts as a link among cancer cells, immune cells, and fibroblasts, the cells that produce structural tissue. The work is now helping shape a first-of-its-kind clinical trial that will combine an IL1RAP-targeted drug with chemoimmunotherapy before surgery in patients whose tumors can still be removed.