| Literature DB >> 32613204 |
Steven M Corsello1,2,3, Rohith T Nagari1, Ryan D Spangler1, Jordan Rossen1, Mustafa Kocak1, Jordan G Bryan1,4, Ranad Humeidi1, David Peck1, Xiaoyun Wu1, Andrew A Tang1, Vickie M Wang1, Samantha A Bender1, Evan Lemire1, Rajiv Narayan1, Philip Montgomery1, Uri Ben-David1,5, Colin W Garvie1, Yejia Chen1, Matthew G Rees1, Nicholas J Lyons1, James M McFarland1, Bang T Wong1, Li Wang1,6, Nancy Dumont1, Patrick J O'Hearn1,7, Eric Stefan1,8, John G Doench1, Caitlin N Harrington1, Heidi Greulich1, Matthew Meyerson1,2,3, Francisca Vazquez1, Aravind Subramanian1, Jennifer A Roth1, Joshua A Bittker1,9, Jesse S Boehm1, Christopher C Mader1,10, Aviad Tsherniak1, Todd R Golub11,12,13,14.
Abstract
Anti-cancer 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, 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 cell lines' molecular features. Our findings include compounds that killed by inducing PDE3A-SLFN12 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 multi-drug resistance protein 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.Entities:
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Year: 2020 PMID： 32613204 PMCID： PMC7328899 DOI： 10.1038/s43018-019-0018-6
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347