Predictive Biomarkers and Personalized Medicine FGFR1 mRNA and Protein Expression, not Gene Copy Number, Predict FGFRTKI Sensitivity across All LungCancer Histologies

Purpose: FGFR1 gene copy number (GCN) is being evaluated as a biomarker for FGFR tyrosine kinase inhibitor (TKI) response in squamous cell lung cancers (SCC). The exclusive use of FGFR1 GCN for predicting FGFR TKI sensitivity assumes increased GCN is the only mechanism for biologically relevant increases in FGFR1 signaling. Herein, we tested whether FGFR1mRNA and protein expressionmay serve as better biomarkers of FGFR TKI sensitivity in lung cancer. ExperimentalDesign:Histologically diverse lung cancer cell lineswere submitted to assays for ponatinib sensitivity, a potent FGFR TKI. A tissue microarray composed of resected lung tumors was submitted to FGFR1 GCN, and mRNA analyses and the results were validated with The Cancer Genome Atlas (TCGA)