Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Nature cancer, 2020-02, Vol.1 (2), p.235

Ort / Verlag

England

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.