Drug-Sensitivity Screening and Genomic Characterization of 45 HPV-Negative Head and Neck Carcinoma Cell Lines for Novel Biomarkers of Drug Efficacy

Abstract

There is an unmet need for effective targeted therapies for patients with advanced head and neck squamous cell carcinoma (HNSCC). We correlated gene expression, gene copy numbers, and point mutations in 45 human papillomavirus-negative HNSCC cell lines with the sensitivity to 220 anticancer drugs to discover predictive associations to genetic alterations. The drug response profiles revealed diverse efficacy of the tested drugs across the cell lines. Several genomic abnormalities and gene expression differences were associated with response to mTOR, MEK, and EGFR inhibitors. <i>NOTCH1</i> and <i>FAT1</i> were the most commonly mutated genes after <i>TP53</i> and also showed some association with response to MEK and/or EGFR inhibitors. <i>MYC</i> amplification and <i>FAM83H</i> overexpression associated with sensitivity to EGFR inhibitors, and <i>PTPRD</i> deletion with poor sensitivity to MEK inhibitors. The connection between high <i>FAM83H</i> expression and responsiveness to the EGFR inhibitor erlotinib was validated by gene silencing and from the data set at the Cancer Cell Line Encyclopedia. The data provide several novel genomic alterations that associated to the efficacy of targeted drugs in HNSCC. These findings require further validation in experimental models and clinical series. <i>Mol Cancer Ther; 17(9); 2060-71. ©2018 AACR</i>.