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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Corsello, SM; Nagari, RT; Spangler, RD; Rossen, J; Kocak, M; Bryan, JG; Humeidi, R; Peck, D; Wu, X; Tang, AA; Wang, VM; Bender, SA; Lemire, E; Narayan, R; Montgomery, P; Ben-David, U; Garvie, CW; Chen, Y; Rees, MG; Lyons, NJ; McFarland, JM; Wong, BT; Wang, L; Dumont, N; O'Hearn, PJ; Stefan, E; Doench, JG; Harrington, CN; Greulich, H; Meyerson, M; Vazquez, F; Subramanian, A; Roth, JA; Bittker, JA; Boehm, JS; Mader, CC; Tsherniak, A; Golub, TR

Published Date

  • February 2020

Published In

Volume / Issue

  • 1 / 2

Start / End Page

  • 235 - 248

PubMed ID

  • 32613204

Pubmed Central ID

  • PMC7328899

Electronic International Standard Serial Number (EISSN)

  • 2662-1347

International Standard Serial Number (ISSN)

  • 2662-1347

Digital Object Identifier (DOI)

  • 10.1038/s43018-019-0018-6

Language

  • eng