Targeting the FGFR signaling pathway in cholangiocarcinoma: promise or delusion?

Cholangiocarcinoma (CCA) is a refractory cancer with limited treatment options and poorly understood molecular mechanisms underlying tumor development. The most effective treatment is surgical resection; however, patients are highly prone to recurrence. Moreover, considering that most patients are diagnosed in advanced stages, treatment options are restricted to palliative care, which results in poor prognosis. Due to the limited effect of chemotherapy and radiotherapy, targeted therapy is becoming a hot topic in the field of biliary cancer treatment. The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway involves a variety of key biological processes for cell survival, differentiation, and metabolism. Next-generation sequencing data mining has shown that high levels of FGF/FGFR expression are associated with reduced overall survival (OS) in CAA, which indicates that the FGF/FGFR pathway may be an effective target for CAA treatment. This paper reviews the effect of FGF/FGFR signaling on CCA from onset to treatment and highlights the promise of FGF/FGFR signaling pathway inhibitors for targeting CCA.

Keywords: cholangiocarcinoma; fibroblast growth factor receptor; targeted therapy; tyrosine kinase inhibitors.