Anticancer uses of non-oncology drugs have occasionally been found, but such discoveries have been serendipitous. We sought to create a public resource containing the growth-inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. We used PRISM (profiling relative inhibition simultaneously in mixtures), a molecular barcoding method, to screen drugs against cell lines in pools. An unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines in a manner predictable from the molecular features of the cell lines. Our findings include compounds that killed by inducing phosphodiesterase 3A-Schlafen 12 complex formation, vanadium-containing compounds whose killing depended on the sulfate transporter SLC26A2, the alcohol dependence drug disulfiram, which killed cells with low expression of metallothioneins, and the anti-inflammatory drug tepoxalin, which killed via the multidrug resistance protein ATP-binding cassette subfamily B member 1 (ABCB1). The PRISM drug repurposing resource (https://depmap.org/repurposing) is a starting point to develop new oncology therapeutics, and more rarely, for potential direct clinical translation.

偶尔会发现非肿瘤药物的抗癌用途，但这些发现都是偶然的。我们试图创建一个公共资源，其中包含在 578 种人类癌细胞系中测试的 4,518 种药物的生长抑制活性。我们使用 PRISM（同时分析混合物中的相对抑制），一种分子条形码方法，针对池中的细胞系筛选药物。出乎意料地大量非肿瘤药物以可从细胞系分子特征预测的方式选择性抑制癌细胞系子集。我们的研究结果包括通过诱导磷酸二酯酶 3A-Schlafen 12 复合物形成而杀死的化合物、依赖硫酸盐转运蛋白 SLC26A2 杀死的含钒化合物、杀死金属硫蛋白低表达细胞的酒精依赖药物双硫仑以及抗炎药物替泊沙林，通过多药耐药蛋白 ATP 结合盒亚家族 B 成员 1 (ABCB1) 杀死。 PRISM 药物再利用资源 (https://depmap.org/repurifying) 是开发新肿瘤疗法的起点，更罕见的是，它是潜在的直接临床转化的起点。