title: Role of the fibroblast growth factor receptor axis in cholangiocarcinoma.
abstract: Advanced cholangiocarcinoma (CCA) is a highly lethal disease with limited therapeutic options beyond cytotoxic chemotherapy. Molecular profiling of CCA has provided insights into the pathogenesis of this disease and identified potential therapeutic targets. The fibroblast growth factor receptor (FGFR) axis is important for maintaining tissue homeostasis. Aberrations in FGFR activity have been implicated in the development and progression of CCA and other malignancies, which has generated significant interest in exploring FGFR's therapeutic potential. FGFR2 fusion events are present in up to 17% of intrahepatic CCAs and appear to predict sensitivity to FGFR inhibitors even after progression on chemotherapy. These observations have led to a clinical trial evaluating FGFR inhibition in patients with CCA enriched for FGFR alterations. This review summarizes current knowledge about the role of the FGFR pathway in cholangiocarcinogenesis and ongoing work in developing FGFR-directed therapies as an antineoplastic strategy for CCA.
authors: Division of Medicine, Hematology, and Medical Oncology, Mount Sinai School of Medicine, New York, New York, USA.
authors: Celina
authors: C
authors: Ang
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives; D000970:Antineoplastic Agents; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000235:genetics*; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000235:genetics*; D002869:Chromosome Aberrations; D055808:Drug Discovery; D050939:Gene Fusion; D006801:Humans; D058990:Molecular Targeted Therapy; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014227:Triazines
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D017468:Receptors, Fibroblast Growth Factor; D014227:Triazines; C568950:infigratinib; C509922:brivanib; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D000409:Alanine
keywords: cholangiocarcinoma; fibroblast growth factor receptor; tyrosine kinase inhibitor