Dovitinib: Rationale, preclinical and early clinical data in urothelial carcinoma of the bladder

Clarisse R. Mazzola, Khurram M. Siddiqui, Michele Billia, Joseph Chin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Original languageEnglish
Pages (from-to)1553-1562
Number of pages10
JournalExpert Opinion on Investigational Drugs
Volume23
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

Fingerprint

Receptor, Fibroblast Growth Factor, Type 3
Urinary Bladder Neoplasms
Urinary Bladder
Carcinoma
Expert Testimony
Neutralizing Antibodies
Protein-Tyrosine Kinases
4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
Monoclonal Antibodies
Mutation
Mortality
Incidence
Therapeutics

Keywords

  • Bladder cancer
  • Clinical trial
  • Dovitinib
  • Phase I trial
  • Phase II trial
  • Preclinical studies
  • Targeted agents
  • TKI-258
  • TKI258
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Dovitinib : Rationale, preclinical and early clinical data in urothelial carcinoma of the bladder. / Mazzola, Clarisse R.; Siddiqui, Khurram M.; Billia, Michele; Chin, Joseph.

In: Expert Opinion on Investigational Drugs, Vol. 23, No. 11, 01.11.2014, p. 1553-1562.

Research output: Contribution to journalArticle

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