New research highlights how sympathetic nerves interact with cancer-associated fibroblasts (CAFs) to fuel pancreatic ductal adenocarcinoma (PDAC), one of the deadliest forms of cancer. The study shows that these nerves actively signal to CAFs, creating a tumor-supporting environment.
Analysis of human PDAC samples revealed that high sympathetic nerve density is linked to faster disease progression and poorer survival, while parasympathetic or sensory nerves are associated with better outcomes. In both humans and mice, CAFs were observed clustering around sympathetic nerve bundles, indicating a close functional relationship.
Researchers created a pancreas-specific genetic model to safely remove sympathetic nerves. In female mice, this “genetic sympathectomy” led to smaller tumors, but male mice showed no benefit, suggesting that nerve-to-cancer signaling may differ by sex, potentially due to hormonal or immune system factors. This discovery opens new avenues for understanding pancreatic cancer biology and developing targeted therapies.