Mutations in the PI3K/AKT/mTOR signaling pathway frequently occur in eCCA (40%) and iCCA (25%), including FBXW7, PI3KCA, PTEN, NF1, NF2, PIK3R1, STK11, TSC1, and TSC2, and are associated with a worse prognosis.58,66 Mutations in PIK3CA are frequent in GBC (8–13%).57,67 PI3K/AKT/mTOR often signals downstream of ErbB/HER and preclinical studies suggest activity of PI3K/AKT/mTOR inhibition in BTCs,68,69 although clinical studies are scarce. This evidence concerns the gene AKT1 and infantile convulsions and choreoathetosis.