期刊
NATURE CANCER
卷 1, 期 2, 页码 235-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s43018-019-0018-6
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资金
- Carlos Slim Foundation (Slim Initiative in Genomic Medicine for the Americas)
- Next Generation Fund at the Broad Institute of MIT and Harvard
- Conquer Cancer Foundation of ASCO Young Investigator Award
- National Institutes of Health [U01 HG008699, U54 HL127366, KL2 TR002542, K08 CA230220]
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.
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