With regard to carcinogenesis of pancreatic ductal adenocarcinoma, well-known molecular alterations occur like telomere shortening, activating mutations in KRAS, inactivating mutations or epigenetic silencing of p16/CDKN2A and inactivating mutations in TP53 and SMAD4 leading to pancreatic intraepithelial neoplasia (PanIn) formation and, finally, to invasive ductal adenocarcinoma (45). Here, SMAD4 is linked to pancreatic ductal adenocarcinoma.