PIK3CA and intrahepatic cholangiocarcinoma: To test whether the aggressiveness of Trp53;Nf2 mutated ICC is dependent on Wnt and AKT signaling directly, we treated mice bearing KRASG12D;Nf2;Trp53-KO tumors with an inhibitor of Porcupine (LGK974), which reduces Wnt ligand secretion by preventing palmitoylation of Wnt ligands and a PI3K inhibitor, pictilisib, which prevents the conversion of PIP2 into PIP3 and thereby reduces AKT phosphorylation.