This is the first report to reveal the biological processes of circRNA-mediated LIF paracrine signaling by CAFs to establish a distinct fibroblast niche mediating GEM resistance in PDAC, suggesting the urgent need for the development of rational strategies that target the circFARP1/CAV1/miR-660-3p/LIF axis in the TME to overcome GEM resistance in pancreatic cancer patients. The gene discussed is CAV1; the disease is familial pancreatic carcinoma.