Drug-induced change in gene expression across NCI-60 cell lines after exposure to 15 anticancer agents for 2, 6 and 24h (5-Azacytidine). Drug-induced change in gene expression across NCI-60 cell lines after exposure to 15 anticancer agents for 2, 6 and 24h (5-Azacytidine)

To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathway–specific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs. Overall design: To compare and contrast transcriptional responses over time, in the NCI-60 cell line panel after treatment with 15 anticancer agents.

为识别不同细胞类型中药物诱导的基因调控模式，我们检测了NCI-60细胞系在暴露于15种抗肿瘤药物后的基因表达变化。研究结果被整合至一个数据库与交互式分析工具集——NCI转录药效动力学工作台（NCI Transcriptional Pharmacodynamics Workbench, NCI TPW），该工具旨在支持基因表达调控的探索分析，涵盖基于分子通路、药物靶点的解析，以及与药物敏感性的关联研究。我们识别出跨药物与细胞类型的共有转录应答特征，并揭示了与药物敏感性相关的细胞信号通路特异性基因表达变化。此外，我们验证了该工具在研究临床相关分子假说中的应用价值：通过NCI TPW分析与免疫功能及上皮间质转化（epithelial-mesenchymal transition, EMT）相关基因的药物诱导表达变化，并筛选出药物活性候选生物标志物。NCI TPW提供了一套全面的研究资源，助力解析决定抗肿瘤药物敏感性的肿瘤细胞特征。整体实验设计：对比15种抗肿瘤药物处理后，NCI-60细胞系面板在不同时间点的转录应答差异。