NVP-LDE-225 and NVP-BEZ-235, alone or in combination, inhibited spheroid formation by pancreatic CSCs isolated from Pankras/p53 mice, suggesting the inhibition of these PI3K/Akt/mTOR and Shh pathways can be exploited in pancreatic cancer harboring mutations in Kras and p53. This evidence concerns the gene MTOR and familial pancreatic carcinoma.