Researchers are closing in on one of the most stubborn molecular drivers of pancreatic cancer. Deep inside tumor cells and the fibrous tissues surrounding them, a fast-acting enzyme called Pin1 rewires signaling pathways that help cancers grow, spread, and evade therapy. A new effort by UC Riverside and City of Hope is using a precision-engineered “molecular crowbar” to pry this enzyme apart and trigger its destruction.⁠ ⁠ The strategy hinges on custom-designed compounds that bind tightly to Pin1, push it into an unstable shape, and mark it for removal by the cell’s own disposal machinery. Instead of simply blocking the enzyme’s activity, these degraders erase the protein entirely, offering a fundamentally different way to dismantle cancer’s internal wiring.⁠ ⁠ To move the approach forward, the teams strengthened the compounds’ stability in blood plasma, then mapped how they affect cancer cells and the surrounding fibroblasts drawn from patient biopsies. That dual targeting is critical, because the tumor microenvironment in pancreatic cancer forms a dense, treatment-resistant barrier that protects malignant cells from chemotherapy and immunotherapy.⁠ ⁠ In mouse models of peritoneal metastases—one of the deadliest complications of pancreatic, gastrointestinal, and abdominal cancers—the degraders sharply reduced tumor burden. The results offer rare proof-of-concept progress against a disease where survival is often measured in months.⁠ ⁠ Backed by a National Cancer Institute cooperative grant, the collaboration is now advancing these degraders toward clinical readiness. Because Pin1 is active across many tumor types, this approach could open a broader therapeutic class built around selective protein dismantling.⁠ ⁠ #tech #biotech #cancerresearch #pancreaticcancer #drugdiscovery #proteindegradation #molecularbiology #innovation #futuremedicine