Data from Kinase Domain Activation of FGFR2 Yields High-Grade Lung Adenocarcinoma Sensitive to a Pan-FGFR Inhibitor in a Mouse Model of NSCLC

Abstract

<div>Abstract<p>Somatic mutations in <i>FGFR2</i> are present in 4% to 5% of patients diagnosed with non–small cell lung cancer (NSCLC). Amplification and mutations in <i>FGFR</i> genes have been identified in patients with NSCLCs, and clinical trials are testing the efficacy of anti-FGFR therapies. <i>FGFR2</i> and other <i>FGFR</i> kinase family gene alterations have been found in both lung squamous cell carcinoma and lung adenocarcinoma, although 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 <i>FGFR2</i>. Combined with p53 ablation, primary grade 3/4 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 pan-FGFR inhibition. This is the first FGFR2-driven lung cancer GEMM, which can be applied across different cancer indications in a preclinical setting. <i>Cancer Res; 74(17); 4676–84. ©2014 AACR</i>.</p></div>