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. NOTCH1 and FAT1 were the most commonly mutated genes after TP53 and also showed some association with response to MEK and/or EGFR inhibitors. MYC amplification and FAM83H overexpression associated with sensitivity to EGFR inhibitors, and PTPRD deletion with poor sensitivity to MEK inhibitors. The connection between high FAM83H 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. Mol Cancer Ther; 17(9); 2060–71. ©2018 AACR.

中文翻译：

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45 种 HPV 阴性头颈癌细胞系的药物敏感性筛选和基因组表征，用于新的药物疗效生物标志物

对晚期头颈部鳞状细胞癌 (HNSCC) 患者的有效靶向治疗的需求尚未得到满足。我们将 45 种人乳头瘤病毒阴性 HNSCC 细胞系中的基因表达、基因拷贝数和点突变与对 220 种抗癌药物的敏感性相关联，以发现与遗传改变的预测关联。药物反应曲线揭示了测试药物在细胞系中的不同功效。一些基因组异常和基因表达差异与对 mTOR、MEK 和 EGFR 抑制剂的反应有关。NOTCH1 和 FAT1 是 TP53 之后最常见的突变基因，并且还显示出与对 MEK 和/或 EGFR 抑制剂的反应有关。MYC 扩增和 FAM83H 过表达与对 EGFR 抑制剂的敏感性相关，和对 MEK 抑制剂敏感性差的 PTPRD 缺失。FAM83H 高表达与对 EGFR 抑制剂厄洛替尼的反应性之间的联系通过基因沉默和来自癌细胞系百科全书的数据集进行了验证。数据提供了几种与靶向药物在 HNSCC 中的疗效相关的新基因组改变。这些发现需要在实验模型和临床系列中进一步验证。摩尔癌症治疗; 17(9); 2060-71。©2018 AACR。这些发现需要在实验模型和临床系列中进一步验证。摩尔癌症治疗; 17(9); 2060-71。©2018 AACR。这些发现需要在实验模型和临床系列中进一步验证。摩尔癌症治疗; 17(9); 2060-71。©2018 AACR。