2. Academic Validation
  3. 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. [email protected].
  • 12 Harvard Medical School, Boston, MA, USA. [email protected].
  • 13 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [email protected].
  • 14 Howard Hughes Medical Institute, Chevy Chase, MD, USA. [email protected].
PMID: 32613204 DOI: 10.1038/s43018-019-0018-6
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.

Figures
Products