1. Academic Validation
  2. Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling

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

  • Nat Cancer. 2020 Feb;1(2):235-248. doi: 10.1038/s43018-019-0018-6.
Steven M Corsello 1 2 3 Rohith T Nagari 1 Ryan D Spangler 1 Jordan Rossen 1 Mustafa Kocak 1 Jordan G Bryan 1 4 Ranad Humeidi 1 David Peck 1 Xiaoyun Wu 1 Andrew A Tang 1 Vickie M Wang 1 Samantha A Bender 1 Evan Lemire 1 Rajiv Narayan 1 Philip Montgomery 1 Uri Ben-David 1 5 Colin W Garvie 1 Yejia Chen 1 Matthew G Rees 1 Nicholas J Lyons 1 James M McFarland 1 Bang T Wong 1 Li Wang 1 6 Nancy Dumont 1 Patrick J O'Hearn 1 7 Eric Stefan 1 8 John G Doench 1 Caitlin N Harrington 1 Heidi Greulich 1 Matthew Meyerson 1 2 3 Francisca Vazquez 1 Aravind Subramanian 1 Jennifer A Roth 1 Joshua A Bittker 1 9 Jesse S Boehm 1 Christopher C Mader 1 10 Aviad Tsherniak 1 Todd R Golub 11 12 13 14
Affiliations

Affiliations

  • 1 Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • 2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • 3 Harvard Medical School, Boston, MA, USA.
  • 4 Duke University, Durham, NC, USA.
  • 5 Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel.
  • 6 10x Genomics, Pleasanton, CA, USA.
  • 7 Relay Therapeutics, Cambridge, MA, USA.
  • 8 Biogen, Cambridge, MA, USA.
  • 9 Vertex Pharmaceuticals, Boston, MA, USA.
  • 10 Flatiron Health, New York, NY, USA.
  • 11 Broad Institute of MIT and Harvard, Cambridge, MA, USA. golub@broadinstitute.org.
  • 12 Harvard Medical School, Boston, MA, USA. golub@broadinstitute.org.
  • 13 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. golub@broadinstitute.org.
  • 14 Howard Hughes Medical Institute, Chevy Chase, MD, USA. golub@broadinstitute.org.
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.

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