REG4 and familial pancreatic carcinoma: For PDAC, Hu et al. showed that the elevated level of COX-2 was activated by EGFR/p38-MAPK/Sp1 signaling axis and led to the angiogenesis [55]; Ma et al. has demonstrated that the transformation of macrophage from M1 to M2 is triggered by pancreatic cancer secreted regenerating family member 4 (REG4) through the EGFR/AKT/CREB (cAMP-response element binding protein) pathway [56].