As far as we know, this is the first study showing that one of several mechanisms of chemoresistance in PaCa cells involves chemokines and their receptor, CXCL12. We have shown that CXCR4 antagonists can inhibit the development of GEM-R PaCa. Here, CXCR4 is linked to permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome.