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Cholangiocarcinomas (CCAs) are heterogeneous tumors arising from the biliary tract with features of cholangiocyte differentiation. CCAs are aggressive tumors with limited treatment options and poor overall survival. Only a subset of CCA patients with early stage disease can avail potentially curative treatment options. For advanced biliary tract tumors, currently there are limited effective treatment modalities. Recent advances have provided greater insight into the genomic landscape of CCAs. The fibroblast growth factor receptor (FGFR) pathway is involved in key cellular processes essential to survival and differentiation. Accordingly, aberrant FGFR signaling has significant oncogenic potential. Recent discovery of FGFR2 gene fusions in CCA has heightened interest in FGFR inhibition in advanced biliary tract cancer. These findings have served as a catalyst for ongoing clinical investigation of FGFR inhibition in CCA patients with various FGFR signaling abnormalities. Herein, we review FGFR aberrations in CCA and their prognostic implications, FGFR targeting as a viable therapeutic option in advanced biliary tract malignancies, and future directions for development of combination approaches utilizing FGFR inhibition.

The rise of the FGFR inhibitor in advanced biliary cancer: the next cover of time magazine?