Abstract 4851: Kinase domain activation of FGFR2 yields high-grade lung adenocarcinoma sensitive to a pan-FGFR inhibitor in a mouse model of NSCLC

Abstract

Abstract Somatic mutations in Fibroblast Growth Factor Receptor 2 (FGFR2) have been found in 4-5% of patients diagnosed with non-small cell lung cancer (NSCLC). FGFR2 and other FGFR kinase family gene alterations have been found in lung squamous cell carcinoma, adenocarcinoma, and other malignancies though mouse models of FGFR driven lung cancers have not been reported. Here, we generated a genetically engineered mouse model (GEMM) of NSCLC driven by a kinase domain mutation in FGFR2. Combined with p53 ablation, primary grade III/IV adenocarcinoma was induced in the lung epithelial compartment exhibiting locally invasive and pleiotropic tendencies largely made up of multinucleated cells. Tumors were acutely sensitive to pharmacological inhibition of FGFR signaling. In preliminary studies tumors also responded to Programmed death pathway immune checkpoint blockade using anti-PD-1 antibody arguing for activated immune evasion mechanisms in this model.This is the first autochthonous FGFR2-driven lung cancer GEMM that can be applied across different cancer indications in a preclinical setting. Citation Format: Esra A. Akbay, Jeremy H. Tchaicha, Abigail Altabef, Oliver R. Mikse, Eiki Kikuchi, Kevin Rhee, Rachel Liao, Roderick T. Bronson, Lynette M. Sholl, Matthew Meyerson, Peter S. Hammerman, Kwok-Kin Wong. Kinase domain activation of FGFR2 yields high-grade lung adenocarcinoma sensitive to a pan-FGFR inhibitor in a mouse model of NSCLC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4851. doi:10.1158/1538-7445.AM2014-4851