Since PI3K can be activated through an initial phosphorylation in response to oncogenic RAS, the PI3K/AKT pathway is frequently activated in human pancreatic cancer and mouse models of KRAS-driven pancreatic cancer.28,59 Abnormal overexpression or activation of AKT is associated with >40% of pancreatic cancer patients. Here, PIK3CA is linked to familial pancreatic carcinoma.