Our results lead us to three novel findings: i) CXCR2 signaling is upregulated during the primitive stages of KRAS(G12D)-induced PDAC development, ii) upregulation of CXCR2 signaling by KRAS(G12D) enhances autonomous proliferation of tumor cell in PDAC, and iii) KRAS(G12D)-induced CXCR2-CXCL axis in tumor cells upregulates the expression of KRAS protein maintaining a feed-forward loop in PDAC cells. The gene discussed is CXCR2; the disease is neoplasm.