Discovering the anticancer potential of non-oncology drugs by systematic viability profiling
Discovering the anticancer potential of non-oncology drugs by systematic viability profiling
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DOI：
10.1038/s43018-019-0018-6
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发表时间：
2020-02-01
期刊：
影响因子：
22.7
通讯作者：
Golub, Todd R.
中科院分区：
文献类型：
--
作者：
Corsello, Steven M.;Nagari, Rohith T.;Golub, Todd R.
非肿瘤药物的抗癌用途偶尔被发现，但这种发现是偶然的。我们试图创建一个公共资源，其中包含在578个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（在混合物中同时分析相对抑制），一种分子条形码方法，来筛选针对池中细胞系的药物。出乎意料的大量非肿瘤药物以从细胞系的分子特征可预测的方式选择性地抑制癌细胞系的亚群。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，其杀死依赖于硫酸盐转运蛋白SLC 26 A2的含钒化合物，酒精依赖药物双硫仑，其杀死金属硫蛋白低表达的细胞，以及抗炎药物替泊沙林，其通过多药耐药蛋白ATP结合盒亚家族B成员1（ABCB 1）杀死。PRISM药物再利用资源（）是开发新的肿瘤治疗方法的起点，更罕见的是，用于潜在的直接临床转化。
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 () is a starting point to develop new oncology therapeutics, and more rarely, for potential direct clinical translation.