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

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

Molecular cancer therapeutics (2013-05-10)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Fibroblast Growth Factor Receptor-3, Cytoplasmic antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Phosphotyrosine Antibody, clone 4G10®, clone 4G10®, Upstate®, from mouse