Advances in targeting FGFR2 for treatment of advanced cholangiocarcinoma / 国际肿瘤学杂志

ABSTRACT

Fibroblast growth factor receptor (FGFR) 2 gene fusion plays an important role in the pathogenesis of cholangiocarcinoma (CCA) . The method of targeting FGFR2 has been listed as the major therapy for advanced CCA. Adenosine triphosphate (ATP) -competitive FGFR inhibitors, represented by infigratinib and pemigatinib, effectively delay tumor progression and prolong patients survival, and are the first-line drugs for advanced CCA patients with FGFR2 fusion. However, almost all the patients treated with infigratinib eventually develop resistance, which require the combination with other drugs. Futibatinib may serve as a later-line drug for advanced CCA patients with V564F mutation after infigratinib resistance. For the infigratinib-resistant CCA patients harboring aberrant activation of the mitogen-activated protein kinase (MAPK) pathway, combination of the MAPK inhibitor or the heat shock protein 90 inhibitor may be considered as a novel therapeutic option.