We first established that autocrine expression of CXCL12 in normal intestinal and breast epithelial cells is epigenetically down-regulated by hypermethylation of the promoter region of its gene [24], [25].Retention of CXCR4 expression in CXCL12 silenced colorectal or breast cancer cells resulted in increased metastatic potential.With over 75% of patients diagnosed with either local or distant metastasis [57],PDACis a highly aggressive form of cancer in need of more effective therapies. The gene discussed is CXCR4; the disease is cancer.