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Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling.
Corsello, Steven M; Nagari, Rohith T; Spangler, Ryan D; Rossen, Jordan; Kocak, Mustafa; Bryan, Jordan G; Humeidi, Ranad; Peck, David; Wu, Xiaoyun; Tang, Andrew A; Wang, Vickie M; Bender, Samantha A; Lemire, Evan; Narayan, Rajiv; Montgomery, Philip; Ben-David, Uri; Garvie, Colin W; Chen, Yejia; Rees, Matthew G; Lyons, Nicholas J; McFarland, James M; Wong, Bang T; Wang, Li; Dumont, Nancy; O'Hearn, Patrick J; Stefan, Eric; Doench, John G; Harrington, Caitlin N; Greulich, Heidi; Meyerson, Matthew; Vazquez, Francisca; Subramanian, Aravind; Roth, Jennifer A; Bittker, Joshua A; Boehm, Jesse S; Mader, Christopher C; Tsherniak, Aviad; Golub, Todd R.
Affiliation
  • Corsello SM; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nagari RT; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Spangler RD; Harvard Medical School, Boston, MA, USA.
  • Rossen J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kocak M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bryan JG; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Humeidi R; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Peck D; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wu X; Duke University, Durham, NC, USA.
  • Tang AA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wang VM; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bender SA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lemire E; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Narayan R; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Montgomery P; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ben-David U; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Garvie CW; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chen Y; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Rees MG; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lyons NJ; Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel.
  • McFarland JM; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wong BT; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wang L; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Dumont N; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • O'Hearn PJ; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Stefan E; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Doench JG; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Harrington CN; 10x Genomics, Pleasanton, CA, USA.
  • Greulich H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Meyerson M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Vazquez F; Relay Therapeutics, Cambridge, MA, USA.
  • Subramanian A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Roth JA; Biogen, Cambridge, MA, USA.
  • Bittker JA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Boehm JS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mader CC; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tsherniak A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Golub TR; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nat Cancer ; 1(2): 235-248, 2020 02.
Article in En | MEDLINE | ID: mdl-32613204
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neoplasms Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Cancer Year: 2020 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neoplasms Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Cancer Year: 2020 Document type: Article Affiliation country: Estados Unidos