Over the past three decades, high-throughput phenotypic cancer cell line screens have revealed unanticipated small-molecule activities and illuminated connections between tumor genotypes and anticancer efficacy. Founded in 1984, the National Cancer Institute’s “NCI60” screen laid the conceptual groundwork for the contemporary landscape of phenotypic drug discovery. NCI60 first operated as a primary bioactivity screen, but molecular characterization of the NCI60 cell line panel and development of a small-molecule sensitivity pattern recognition algorithm (called “COMPARE”) have enabled subsequent studies into drug mechanisms of action and biomarker identification. In this issue of Cancer Research, Kunkel and colleagues report an updated version of the NCI60 screen, dubbed “HTS384” NCI60, that better aligns with current cell proliferation assay standards and has higher throughput. Changes include the use of a 384-well plate format, automated laboratory equipment, 3 days of compound exposure, and a CellTiter-Glo luminescent endpoint. To confirm that data from the HTS384 and classic NCI60 screen are comparable, the authors tested a library of 1,003 anticancer agents using both protocols and applied COMPARE to analyze patterns of cell line sensitivities. More than three dozen groups of targeted therapies showed high comparability between screens. Modernization of NCI60, and closer integration with other large-scale pharmacogenomic screens and molecular feature sets, will help this public screening service remain pertinent for cancer drug discovery efforts for years to come. See related article by Kunkel et al., p. 2403

中文翻译：

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现代化 NCI60 细胞系筛选以促进 21 世纪表型药物发现


在过去的三十年中，高通量表型癌细胞系筛选揭示了意想不到的小分子活性，并阐明了肿瘤基因型与抗癌功效之间的联系。美国国家癌症研究所的“NCI60”筛选成立于 1984 年，为当代表型药物发现奠定了概念基础。 NCI60 最初作为主要生物活性筛选，但 NCI60 细胞系组的分子表征和小分子敏感性模式识别算法（称为“COMPARE”）的开发使得后续对药物作用机制和生物标志物识别的研究成为可能。在本期《癌症研究》中，Kunkel 及其同事报告了 NCI60 筛选的更新版本，称为“HTS384”NCI60，它更好地符合当前的细胞增殖测定标准，并且具有更高的通量。变化包括使用 384 孔板格式、自动化实验室设备、3 天的化合物暴露以及 CellTiter-Glo 发光终点。为了确认 HTS384 和经典 NCI60 筛选的数据具有可比性，作者使用这两种方案测试了包含 1,003 种抗癌药物的库，并应用 COMPARE 来分析细胞系敏感性模式。超过三打的靶向治疗组在屏幕之间显示出高度的可比性。 NCI60 的现代化以及与其他大规模药物基因组筛选和分子特征集的更紧密整合，将有助于这项公共筛选服务在未来几年与癌症药物发现工作保持相关性。参见 Kunkel 等人的相关文章，第 17 页。 2403