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Advances in Urology
Volume 2012 (2012), Article ID 429213, 10 pages
http://dx.doi.org/10.1155/2012/429213
Review Article

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

1Section of Experimental Oncology, Leeds Institute of Molecular Medicine, St James’s University Hospital, Leeds LS9 7TF, UK
2Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK

Received 31 May 2012; Accepted 17 June 2012

Academic Editor: Nan-Haw Chow

Copyright © 2012 Erica di Martino et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.