Abstract 4326: Co-amplification of FGF receptors and ligands in FGFR inhibitor-sensitive cell lines

Abstract

Abstract The fibroblast growth factor receptors (FGFR) play a key role during development and in adult function. FGFRs belong to a family of receptor tyrosine kinases which are single-pass transmembrane receptors with extracellular ligand binding domains and an intracellular tyrosine kinase domain. Upon binding of the ligand the kinase domain activates intracellular signaling networks that coordinate cellular processes such as proliferation, growth, differentiation, migration and survival. Fibroblast growth factors (FGFs) are a family of 18 ligands which are able to bind and activate distinct FGFRs. Deregulated FGFR activity, through mutations or translocations, is often associated with oncogenic events. Overexpression of FGFR or FGF may lead to increased cell proliferation, growth, differentiation, migration or survival, thus making it an interesting target. In this study we optimized a TaqMan qRT-PCR-based approach to evaluate the copy number variation for several FGFRs (FGFR1, FGFR2, FGFR3 and FGFR4) and several FGF ligands (FGF1, FGF2, FGF3, FGF4, FGF10, FGF12, and FGF19) on a panel of 23 cell lines. The cell types covered a variety of diseases including bladder, breast, endometrial, gastric, kidney, liver, lymphoma, melanoma, sarcoma, small cell lung carcinoma and squamous cell carcinoma. These cell lines had been tested for sensitivity to the JNJ FGFR small molecule inhibitor JNJ42541707 which is a pan-FGFR inhibitor. We observed in the sensitive (IC50<100nm) and moderately sensitive (IC50 100 nM - 1000 nM) cell lines a co-amplification of FGF receptor and ligand. Two of the most sensitive cell lines to FGFR inhibitor treatments had the greatest amplification of FGFR2 with a copy number value greater than 100. This finding that co-amplification occurs in receptor and ligand offers a new potential biomarker for patients that may be sensitive to small molecule FGFR inhibitors. Citation Format: Katherine Bell, Dana Gaffney, Gabriela Martinez-Cardona, Jayaprakash Karkera, Suso Platero. Co-amplification of FGF receptors and ligands in FGFR inhibitor-sensitive cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4326. doi:10.1158/1538-7445.AM2015-4326