The NCI60 human tumor cell line screen has been in operation as a service to the cancer research community for more than 30 years. The screen operated with 96-well plates, a 2-day exposure period to test agents, and following cell fixation, a visible absorbance endpoint by the protein-staining dye sulforhodamine B. In this study, we describe the next phase of this important cancer research tool, the HTS384 NCI60 screen. Although the cell lines remain the same, the updated screen is performed with 384-well plates, a 3-day exposure period to test agents, and a luminescent endpoint to measure cell viability based upon cellular ATP content. In this study, a library of 1,003 FDA-approved and investigational small-molecule anticancer agents was screened by the two NCI60 assays. The datasets were compared with a focus on targeted agents with at least six representatives in the library. For many agents, including inhibitors of EGFR, BRAF, MEK, ERK, and PI3K, the patterns of GI50 values were very similar between the screens with strong correlations between those patterns within the dataset from each screen. However, for some groups of targeted agents, including mTOR, BET bromodomain, and NAMPRTase inhibitors, there were limited or no correlations between the two datasets, although the patterns of GI50 values and correlations between those patterns within each dataset were apparent. Beginning in January 2024, the HTS384 NCI60 screen became the free screening service of the NCI to facilitate drug discovery by the cancer research community. Significance: The new NCI60 cell line screen HTS384 shows robust patterns of response to oncology agents and substantial overlap with the classic screen, providing an updated tool for studying therapeutic agents. See related commentary by Colombo and Corsello, p. 2397.

中文翻译：

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HTS384 NCI60：NCI60 屏幕的下一阶段。


NCI60 人类肿瘤细胞系筛选作为癌症研究界的一项服务已经运行了 30 多年。该屏幕使用 96 孔板进行操作，测试试剂暴露时间为 2 天，细胞固定后，蛋白质染色染料磺胺罗丹明 B 产生可见的吸光度终点。在这项研究中，我们描述了这种重要癌症的下一阶段研究工具，HTS384 NCI60 屏幕。尽管细胞系保持不变，但更新的筛选是使用 384 孔板、测试剂暴露 3 天的时间以及根据细胞 ATP 含量测量细胞活力的发光终点进行的。在这项研究中，通过两种 NCI60 检测筛选了 1,003 种经 FDA 批准和研究的小分子抗癌药物库。将数据集与图书馆中至少有六名代表的目标代理进行比较。对于许多药物，包括 EGFR、BRAF、MEK、ERK 和 PI3K 抑制剂，屏幕之间的 GI50 值模式非常相似，每个屏幕数据集中的这些模式之间具有很强的相关性。然而，对于某些靶向药物组，包括 mTOR、BET 溴结构域和 NAMPRTase 抑制剂，尽管 GI50 值的模式以及每个数据集中这些模式之间的相关性很明显，但两个数据集之间的相关性有限或没有相关性。从 2024 年 1 月开始，HTS384 NCI60 筛查成为 NCI 的免费筛查服务，以促进癌症研究界的药物发现。意义：新的 NCI60 细胞系筛选 HTS384 显示出对肿瘤药物的稳健反应模式，并且与经典筛选有大量重叠，为研究治疗药物提供了更新的工具。 参见 Colombo 和 Corsello 的相关评论，第 17 页。 2397.