Abstract 4586: Essential role of fibroblast growth factor receptor 2 (FGFR2) in tumorigenesis of human cancers with activated FGFR2 signaling demonstrated by functional blocking antibodies

Abstract

Abstract Aberrant activation of fibroblast growth factor receptor 2 (FGFR2) signaling, through overexpression of FGFR2 and/or its ligands, mutations, and receptor amplification have been found in a variety of human tumors. We generated monoclonal antibodies against the extracellular ligand binding domain of FGFR2 to address the role of FGFR2 in tumorigenesis and to explore the potential of FGFR2 as a novel therapeutic target. We identified a broad panel of human cancer cell lines with dysregulated FGFR2 signaling and examined the sensitivity of these human cell lines to monoclonal antibodies specifically targeting FGFR2. These FGFR2 antibodies potently suppressed ligand-induced phosphorylation of FGFR2 and downstream signaling, as well as cell proliferation in vitro. The administration of FGFR2 monoclonal antibodies in mice significantly inhibited the growth of human cancer xenografts harboring activated FGFR2 signaling. Our findings support that dysregulated FGFR2 signaling is one of the critical oncogenic pathways involved in the initiation and/or maintenance of tumors. Cancer patients with aberrantly activated/amplified FGFR2 signaling could potentially benefit from therapeutic intervention with FGFR2-targeting antibodies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4586. doi:10.1158/1538-7445.AM2011-4586