Research Programs Unit, Laboratory of Molecular Oncology, Translational Cancer Biology Program, University of Helsinki, Helsinki, Finland.
Research Programs Unit, Genome-Scale Biology Program and Medicum, Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland.
Mol Cancer Ther. 2018 Sep;17(9):2060-2071. doi: 10.1158/1535-7163.MCT-17-0733. Epub 2018 Jul 3.
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. and were the most commonly mutated genes after and also showed some association with response to MEK and/or EGFR inhibitors. amplification and overexpression associated with sensitivity to EGFR inhibitors, and deletion with poor sensitivity to MEK inhibitors. The connection between high 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. .
目前，针对晚期头颈部鳞状细胞癌（HNSCC）患者，仍存在未满足的有效靶向治疗需求。我们对 45 例人乳头瘤病毒阴性 HNSCC 细胞系中的基因表达、基因拷贝数和点突变与 220 种抗癌药物的敏感性进行了相关性分析，以发现与遗传改变相关的预测关联。药物反应谱揭示了测试药物在细胞系中的不同疗效。一些基因组异常和基因表达差异与 mTOR、MEK 和 EGFR 抑制剂的反应相关。在 之后， 和 是最常见的突变基因，并且还与 MEK 和/或 EGFR 抑制剂的反应有一定的关联。 扩增和 过表达与 EGFR 抑制剂的敏感性相关，而 缺失与 MEK 抑制剂的敏感性较差相关。高 表达与 EGFR 抑制剂厄洛替尼的反应性之间的联系通过基因沉默和癌症细胞系百科全书的数据得到了验证。这些数据提供了几种与 HNSCC 靶向药物疗效相关的新的基因组改变。这些发现需要在实验模型和临床系列中进一步验证。
