Abstract C63: Targeting FGFR3 with monoclonal antibody impairs bladder cancer growth in vivo.

Abstract

Abstract Fibroblast growth factor receptor 3 (FGFR3) belongs to a family of receptor tyrosine kinases that control cell proliferation, differentiation, and survival. Mutational activation of FGFR3 has been reported in about 50–60% low grade and 15–20% muscle-invasive bladder cancer. FGFR3 is also overexpressed in about 50% of muscle invasive bladder cancer, suggesting a potential role for this receptor in the early stage of bladder carcinogenesis. However, the expression pattern of FGFR3 and its functional importance in metastatic bladder cancer remain to be determined. Using immunohistochemistry, we have found that FGFR3 is overexpressed in 8/13 cases (about 62%) of lymph-node metastasis of bladder cancer. Extensive in vivo efficacy studies with an FGFR3-specific affinity-matured human monoclonal antibody (designated R3Mab) show that R3Mab as a single agent blocks FGFR3 signaling and suppresses the growth of multiple bladder tumor xenografts in mice. Importantly, R3Mab further enhances the anti-tumor activity of chemotherapeutics including gemcitabine and carboplatin. These results demonstrate that FGFR3 is required for the maintenance of bladder cancer of various stages, and support the clinical development of R3Mab in locally advanced and metastatic bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C63.