FGFR Inhibitors in Cholangiocarcinoma—A Novel Yet Primary Approach: Where Do We Stand Now and Where to Head Next in Targeting This Axis?

Abstract

Cholangiocarcinomas (CCAs) are rare but aggressive tumours with poor diagnosis and limited treatment options. Molecular targeted therapies became a promising proposal for patients after progression under first-line chemical treatment. In light of an escalating prevalence of CCA, it is crucial to fully comprehend its pathophysiology, aetiology, and possible targets in therapy. Such knowledge would play a pivotal role in searching for new therapeutic approaches concerning diseases’ symptoms and their underlying causes. Growing evidence showed that fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) pathway dysregulation is involved in a variety of processes during embryonic development and homeostasis as well as tumorigenesis. CCA is known for its close correlation with the FGF/FGFR pathway and targeting this axis has been proposed in treatment guidelines. Bearing in mind the significance of molecular targeted therapies in different neoplasms, it seems most reasonable to move towards intensive research and testing on these in the case of CCA. However, there is still a need for more data covering this topic. Although positive results of many pre-clinical and clinical studies are discussed in this review, many difficulties lie ahead. Furthermore, this review presents up-to-date literature regarding the outcomes of the latest clinical data and discussion over future directions of FGFR-directed therapies in patients with CCA.

Molecular Profile of Intrahepatic Cholangiocarcinoma

“…Infigratinib is an FGFR1–3 -selective inhibitor and showed a 23% objective response rate in an open-label single-arm trial [ 75 ]. Other potential FGFR inhibitors for ICC include Futibatinib, Ponatinib, Erdafitinib, and Debio 1347 [ 76 ].…”