Journal Article

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

Chen, Yejia, Bender, Samantha A, Wang, Li, Rossen, Jordan, Kocak, Mustafa, O'Hearn, Patrick J, Dumont, Nancy, Golub, Todd R, Tang, Andrew A, Wu, Xiaoyun, Narayan, Rajiv, Vazquez, Francisca, Harrington, Caitlin N, Ben-David, Uri, Boehm, Jesse S, Subramanian, Aravind, Stefan, Eric, Peck, David, Roth, Jennifer A, Greulich, Heidi, Rees, Matthew G, McFarland, James M, Montgomery, Philip, Nagari, Rohith T, Doench, John G, Bittker, Joshua A, Spangler, Ryan D, Humeidi, Ranad, Meyerson, Matthew, Bryan, Jordan G, Garvie, Colin W, Corsello, Steven M, Wong, Bang T, Tsherniak, Aviad, Lyons, Nicholas J, Wang, Vickie M, Lemire, Evan, Mader, Christopher C

2020

Overview

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.

• Subject: Cell Line / Disulfiram / Drug Repositioning / Humans / Neoplasms - drug therapy