KRAS and pancreatic ductal adenocarcinoma: A central role of p16 in pancreatic carcinogenesis was firmly established from the analysis of clinical specimens and corroborated by subsequent genetic studies in mice, as tissue-specific oncogenic activation of K-ras in Ink4a/ARF−/− or Ink4A−/−/ARF +/+ mice, but not in wild-type mice resulted in pancreatic ductal adenocarcinoma (Aguirre et al, 2003; Bardeesy et al, 2006).