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

被引：505

作者：

Corsello, Steven M. ^{[1
,2
,3
]}

Nagari, Rohith T. ^{[1
]}

Spangler, Ryan D. ^{[1
]}

Rossen, Jordan ^{[1
,6
]}

Kocak, Mustafa ^{[1
]}

Bryan, Jordan G. ^{[1
]}

Humeidi, Ranad ^{[1
]}

Peck, David ^{[1
]}

Wu, Xiaoyun ^{[1
]}

Tang, Andrew A. ^{[1
]}

Wang, Vickie M. ^{[1
]}

Bender, Samantha A. ^{[1
]}

Lemire, Evan ^{[1
]}

Narayan, Rajiv ^{[1
]}

Montgomery, Philip ^{[1
]}

Ben-David, Uri ^{[1
,7
]}

Garvie, Colin W. ^{[1
]}

Chen, Yejia ^{[1
]}

Rees, Matthew G. ^{[1
]}

Lyons, Nicholas J. ^{[1
]}

McFarland, James M. ^{[1
]}

Wong, Bang T. ^{[1
]}

Wang, Li ^{[1
,8
]}

Dumont, Nancy ^{[1
]}

O'Hearn, Patrick J. ^{[1
,9
]}

Stefan, Eric ^{[10
]}

Doench, John G. ^{[1
]}

Harrington, Caitlin N. ^{[1
]}

Greulich, Heidi ^{[1
]}

Meyerson, Matthew ^{[1
,2
,3
]}

Vazquez, Francisca ^{[1
]}

Subramanian, Aravind ^{[1
]}

Roth, Jennifer A. ^{[1
]}

Bittker, Joshua A. ^{[1
,11
]}

Boehm, Jesse S. ^{[1
]}

Mader, Christopher C. ^{[1
,12
]}

Tsherniak, Aviad ^{[1
]}

Golub, Todd R. ^{[1
,3
,4
,5
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Harvard Med Sch, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[5] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[6] Duke Univ, Durham, NC USA

[7] Tel Aviv Univ, Dept Human Mol Genet & Biochem, Tel Aviv, Israel

[8] 10x Genomics, Pleasanton, CA USA

[9] Relay Therapeut, Cambridge, MA USA

[10] Biogen, Cambridge, MA USA

[11] Vertex Pharmaceut, Boston, MA USA

[12] Flatiron Hlth, New York, NY USA

来源：

NATURE CANCER | 2020年 / 1卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CANCER; IDENTIFICATION; DISULFIRAM; SENSITIVITY; RESISTANCE; LANDSCAPE;

D O I：

10.1038/s43018-019-0018-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Anticancer 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 (profiling relative inhibition simultaneously in mixtures), 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 molecular features of the cell lines. Our findings include compounds that killed by inducing phosphodiesterase 3A-Schlafen 12 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 multidrug resistance protein ATP-binding cassette subfamily B member 1 (ABCB1). The PRISM drug repurposing resource () is a starting point to develop new oncology therapeutics, and more rarely, for potential direct clinical translation.

引用

页码：235 / +

页数：25

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