Novel therapeutic targets in bladder cancer: mutation and expression of FGF receptors.

Bladder cancer presents several challenges in clinical management. For the large group of noninvasive tumors, key problems are the development of multiple recurrences that require long-term surveillance and a lack of effective therapies to prevent recurrence. For the smaller group of poor prognosis patients with invasive disease, novel therapies are urgently needed. The identification of mutations of FGF receptor 3 (FGFR3) in most noninvasive bladder tumors and the recent finding of overexpression of this receptor not only in superficial tumors but also in many invasive bladder cancers has generated optimism that therapies targeting this receptor tyrosine kinase may have major application in the treatment of urothelial cancers. There is little information on the other members of this receptor family apart from FGFR2, which is implicated as a tumor suppressor. Recent preclinical evaluations of FGFR3 as a therapeutic target have provided a strong impetus for the development of targeted agents for clinical use.