The COX-2-selective inhibitor celebrex normalized elevated GTP-Ras levels in K5 COX-2 mice15 despite wild-type K-Ras sequences in pancreatic cancer-relevant codons 12, 13, and 61 (SFig. 1) as well as in BxPC3 cells in vitro (SFig. 8) and in accordance, relative GTP-Ras levels as well as phosphorylated ERK-1,2 were higher in pancreatic ducts of early stage lesions of the CPK mutants than in the PK mutant. Here, PIK3C2A is linked to familial pancreatic carcinoma.