However, it has not been reported whether the activated CXCL12–CXCR4 signaling axis plays an important role in PaCa cells’ resistance to GEM and whether CXCR4 antagonists can inhibit the activated signaling axis in GEM-resistant (GEM-R) PaCa in vitro and in vivo. The gene discussed is CXCR4; the disease is permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome.