A Decade of FGF Receptor Research in Bladder Cancer : Past, Present, and Future Challenges

Abstract EN

Fibroblast growth factors (FGFs) orchestrate a variety of cellular functions by binding to their transmembrane tyrosine-kinase receptors (FGFRs) and activating downstream signalling pathways, including RAS/MAPK, PLCγ1, PI3K, and STATs.

In the last ten years, it has become clear that FGF signalling is altered in a high proportion of bladder tumours.

Activating mutations and/or overexpression of FGFR3 are common in urothelial tumours with low malignant potential and low-stage and -grade urothelial carcinomas (UCs) and are associated with a lower risk of progression and better survival in some subgroups.

FGFR1 is not mutated in UC, but overexpression is frequent in all grades and stages and recent data indicate a role in urothelial epithelial-mesenchymal transition.

In vitro and in vivo studies have shown that FGFR inhibition has cytotoxic and/or cytostatic effects in FGFR-dependent bladder cancer cells and FGFR-targeted agents are currently being investigated in clinical studies for the treatment of UC.

Urine-based tests detecting common FGFR3 mutations are also under development for surveillance of low-grade and -stage tumours and for general population screening.

Overall, FGFRs hold promise as therapeutic targets, diagnostic and prognostic markers, and screening tools for early detection and clinical management of UC.