FGFR2 and cholangiocarcinoma: Specifically, in CCA patients under treatment with FGFRinhibitors, the PI3K/AKT pathway has been reported to convey secondary resistance.46 This is in line with pre-clinical data from other tumor entities thatharbored genetic FGFR1, FGFR2 or FGFR3 alterations, and developed AKT-mediatedresistance after initially responding to FGFR inhibitors.49, –51 It is well conceivable that aconsiderable overlap exists between mechanisms that lead to off-target resistanceand those that cause primary resistance.