title: Dovitinib: rationale, preclinical and early clinical data in urothelial carcinoma of the bladder.
abstract: BACKGROUND
  Bladder cancer (BC) is the third and fifth cancer in men in terms of incidence and mortality in the US. Overexpression and mutations of fibroblast growth factor receptor 3 (FGFR3) are frequently found in BC and can represent a very interesting therapeutic target. Different FGFR3-targeted strategies have been investigated through in vitro and in vivo settings, including FGFR3 tyrosine kinase inhibitors such as dovitinib .
  
  
  METHODS
  The authors review the data that provide a scientific rationale for FGFR3-targeted therapy in BC. They also provide an evaluation of the currently available in vitro and in vivo data on the use of dovitinib in BC patients.
  
  
  CONCLUSIONS
  The development and progression of BC rely on a very complex signaling network that involves many different receptors aside from FGFR3 and VEGFR2. The involved signaling network can also be very different from one BC to the other, and can also evolve through time in the same patient. Inhibiting only one single target may thus not be sufficient to achieve a complete downstream oncogenic signaling blockage. Additionally, in vitro data on the use of neutralizing monoclonal antibodies targeting FGFR3 show that it can be a more efficient strategy to reach the same goal, with the potential advantage of less toxicity.
authors.affiliation: Western University, Division of Urology and Division of Surgical Oncology , London, Ontario , Canada +519 685 8451 ; +519 685 8455 ; joseph.chin@lhsc.on.ca.
authors.forename: Clarisse R
authors.initials: CR
authors.lastname: Mazzola
authors.forename: Khurram M
authors.initials: KM
authors.lastname: Siddiqui
authors.forename: Michele
authors.initials: M
authors.lastname: Billia
authors.forename: Joseph
authors.initials: J
authors.lastname: Chin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: C500007:4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D015363:Quinolones; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: Phase I trial; Phase II trial; TKI-258; TKI258; bladder cancer; clinical trial; dovitinib; preclinical studies; targeted agents; urothelial carcinoma