Fibroblast growth factor receptor 3 is a rational therapeutic target in bladder cancer

Kilian M. Gust, David J. McConkey, Shannon Awrey, Paul K. Hegarty, Jing Qing, Jolanta Bondaruk, Avi Ashkenazi, Bogdan Czerniak, Colin P. Dinney, Peter C. Black

Research output: Contribution to journalArticle

Abstract

Activating mutations of fibroblast growth factor receptor-3 (FGFR3) have been described in approximately 75% of low-grade papillary bladder tumors. In muscle-invasive disease, FGFR3 mutations are found in 20% of tumors, but overexpression of FGFR3 is observed in about half of cases. Therefore, FGFR3 is a particularly promising target for therapy in bladder cancer. Up to now, most drugs tested for inhibition of FGFR3 have been small molecule, multityrosine kinase inhibitors. More recently, a specific inhibitory monoclonal antibody targeting FGFR3 (R3Mab) has been described and tested preclinically. In this study, we have evaluated mutation and expression status of FGFR3 in 19 urothelial cancer cell lines and a cohort of 170 American patients with bladder cancer. We have shown inhibitory activity of R3Mab on tumor growth and corresponding cell signaling in three different orthotopic xenografts of bladder cancer. Our results provide the preclinical proof of principle necessary to translate FGFR3 inhibition with R3Mab into clinical trials in patients with bladder cancer.

Original languageEnglish (US)
Pages (from-to)1245-1254
Number of pages10
JournalMolecular cancer therapeutics
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gust, K. M., McConkey, D. J., Awrey, S., Hegarty, P. K., Qing, J., Bondaruk, J., Ashkenazi, A., Czerniak, B., Dinney, C. P., & Black, P. C. (2013). Fibroblast growth factor receptor 3 is a rational therapeutic target in bladder cancer. Molecular cancer therapeutics, 12(7), 1245-1254. https://doi.org/10.1158/1535-7163.MCT-12-1150