文章目录

通过系统的生存能力分析发现非肿瘤药物的抗癌潜力

原文发布日期：2020-01-20

英文摘要：

摘要翻译：

原文链接：

文章：

通过系统的生存能力分析发现非肿瘤药物的抗癌潜力

Discovering the anticancer potential of non-oncology drugs by systematic viability profiling

原文发布日期：2020-01-20

英文摘要：

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.

摘要翻译：

虽然非癌症药物偶尔被发现具有抗癌活性，但这类发现多为意外所得。我们致力于创建一个公共资源，其中包含针对578种人类癌细胞系测试的4,518种药物的生长抑制活性。为此，我们采用了PRISM（同时在混合物中进行药物筛选的分子条形码方法），这种方法用于对药物在细胞群池中的筛选。出人意料的是，大量非癌症药物具有特定选择性地抑制癌细胞系的能力，并且这种效果可以通过癌细胞系的分子特征进行预测。我们的研究结果包括通过诱导磷酯酶3A- Schlafen 12复合物形成而被杀死的化合物、依赖硫酸转运体SLC26A2而被 Vanadium 类化合物所依赖杀死的化合物，酒精依赖药 disulfiram（用于杀死低表达金属lothioneins 的细胞），以及抗炎药 tepoxalin（通过多药 resistance 蛋白 ATP-binding cassette 子家族 B 成员 1 [ABCB1] 而被杀死）。PRISM药物复用资源（https://depmap.org/repurposing）是一个开发新抗癌药物的起点，并且更罕见地可能具有直接临床应用潜力。