Combination therapies for targeting FGFR2 fusions in cholangiocarcinoma

Fibroblast growth factor receptor 2 (FGFR2) fusion proteins (FFs) are oncogenic drivers in 10-15% of intrahepatic cholangiocarcinoma (iCCA). FGFR-specific inhibitors provide temporary benefit in FF+ unresectable patients. Recent work with mouse iCCA models has documented the necessary role of RAS-ERK downstream to FFs and provided examples of preclinical experimentation aimed at improving FF targeting in iCCA.