Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
entrez:
3
7
2020
pubmed:
3
7
2020
medline:
3
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32613204
doi: 10.1038/s43018-019-0018-6
pmc: PMC7328899
mid: NIHMS1589633
pii: 10.1038/s43018-019-0018-6
doi:
Substances chimiques
Disulfiram
TR3MLJ1UAI
Banques de données
figshare
['10.6084/m9.figshare.9393293', '10.6084/m9.figshare.10277810']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
235-248Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002542
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA230220
Pays : United States
Organisme : NHLBI NIH HHS
ID : U54 HL127366
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008699
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG008097
Pays : United States
Commentaires et corrections
Type : CommentIn
Déclaration de conflit d'intérêts
COMPETING INTERESTS S.M.C, X.W., H.G, M.M., A.S., and T.R.G receive research funding unrelated to this project from Bayer HealthCare. M.M receives research funding from Ono and serves as a scientific advisory board and consultant for OrigiMed. M.M. has patents licensed to LabCorp and Bayer. M.M. and T.R.G. were formerly consultants and equity holders in Foundation Medicine, acquired by Roche. J.A.B. is an employee and shareholder of Vertex Pharmaceuticals. J.G.D. and A.T. consult for Tango Therapeutics. T.R.G. is a consultant to GlaxoSmithKline and is a founder of Sherlock Biosciences. Patent applications for the drug uses detailed in this manuscript have been filed. Other authors declare no competing interests.
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