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

Steven M. Corsello; Rohith T. Nagari; Ryan D. Spangler; Jordan Rossen; Mustafa Kocak; Jordan G. Bryan; Ranad Humeidi; David Peck; Xiaoyun Wu; Andrew A. Tang; Vickie M. Wang; Samantha A. Bender; Evan Lemire; Rajiv Narayan; Philip Montgomery; Uri Ben-David; Colin W. Garvie; Yejia Chen; Matthew G. Rees; Nicholas J. Lyons; James M. McFarland; Bang T. Wong; Li Wang; Nancy Dumont; Patrick J. O'Hearn; Eric Stefan; John G. Doench; Caitlin N. Harrington; Heidi Greulich; Matthew Meyerson; Francisca Vazquez; Aravind Subramanian; Jennifer A. Roth; Joshua A. Bittker; Jesse S. Boehm; Christopher C. Mader; Aviad Tsherniak; Todd R. Golub

doi:https://doi.org/10.1038/s43018-019-0018-6

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

Steven M. Corsello, Rohith T. Nagari, Ryan D. Spangler, Jordan Rossen, Mustafa Kocak, Jordan G. Bryan, Ranad Humeidi, David Peck, Xiaoyun Wu, Andrew A. Tang, Vickie M. Wang, Samantha A. Bender, Evan Lemire, Rajiv Narayan, Philip Montgomery, Uri Ben-David, Colin W. Garvie, Yejia Chen, Matthew G. Rees, Nicholas J. LyonsJames M. McFarland, Bang T. Wong, Li Wang, Nancy Dumont, Patrick J. O'Hearn, Eric Stefan, John G. Doench, Caitlin N. Harrington, Heidi Greulich, Matthew Meyerson, Francisca Vazquez, Aravind Subramanian, Jennifer A. Roth, Joshua A. Bittker, Jesse S. Boehm, Christopher C. Mader, Aviad Tsherniak, Todd R. Golub

Human Molecular Genetics Biochemistry

Tel Aviv University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	235-248
Number of pages	14
Journal	Nature Cancer
Volume	1
Issue number	2
DOIs	https://doi.org/10.1038/s43018-019-0018-6
State	Published - 1 Feb 2020

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

https://doi.org/10.1038/s43018-019-0018-6

Cite this

Corsello, S. M., Nagari, R. T., Spangler, R. D., Rossen, J., Kocak, M., Bryan, J. G., Humeidi, R., Peck, D., Wu, X., Tang, A. A., Wang, V. M., Bender, S. A., Lemire, E., Narayan, R., Montgomery, P., Ben-David, U., Garvie, C. W., Chen, Y., Rees, M. G., ... Golub, T. R. (2020). Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling. Nature Cancer, 1(2), 235-248. https://doi.org/10.1038/s43018-019-0018-6

@article{f610cd95a23a45afa33766dca35e830e,

title = "Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling",

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.",

author = "Corsello, {Steven M.} and Nagari, {Rohith T.} and Spangler, {Ryan D.} and Jordan Rossen and Mustafa Kocak and Bryan, {Jordan G.} and Ranad Humeidi and David Peck and Xiaoyun Wu and Tang, {Andrew A.} and Wang, {Vickie M.} and Bender, {Samantha A.} and Evan Lemire and Rajiv Narayan and Philip Montgomery and Uri Ben-David and Garvie, {Colin W.} and Yejia Chen and Rees, {Matthew G.} and Lyons, {Nicholas J.} and McFarland, {James M.} and Wong, {Bang T.} and Li Wang and Nancy Dumont and O'Hearn, {Patrick J.} and Eric Stefan and Doench, {John G.} and Harrington, {Caitlin N.} and Heidi Greulich and Matthew Meyerson and Francisca Vazquez and Aravind Subramanian and Roth, {Jennifer A.} and Bittker, {Joshua A.} and Boehm, {Jesse S.} and Mader, {Christopher C.} and Aviad Tsherniak and Golub, {Todd R.}",

year = "2020",

month = feb,

day = "1",

doi = "https://doi.org/10.1038/s43018-019-0018-6",

language = "الإنجليزيّة",

volume = "1",

pages = "235--248",

journal = "Nature Cancer",

issn = "1474-175X",

publisher = "Nature Publishing Group",

number = "2",

}

Corsello, SM, Nagari, RT, Spangler, RD, Rossen, J, Kocak, M, Bryan, JG, Humeidi, R, Peck, D, Wu, X, Tang, AA, Wang, VM, Bender, SA, Lemire, E, Narayan, R, Montgomery, P, Ben-David, U, Garvie, CW, Chen, Y, Rees, MG, Lyons, NJ, McFarland, JM, Wong, BT, Wang, L, Dumont, N, O'Hearn, PJ, Stefan, E, Doench, JG, Harrington, CN, Greulich, H, Meyerson, M, Vazquez, F, Subramanian, A, Roth, JA, Bittker, JA, Boehm, JS, Mader, CC, Tsherniak, A & Golub, TR 2020, 'Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling', Nature Cancer, vol. 1, no. 2, pp. 235-248. https://doi.org/10.1038/s43018-019-0018-6

TY - JOUR

T1 - Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling

AU - Corsello, Steven M.

AU - Nagari, Rohith T.

AU - Spangler, Ryan D.

AU - Rossen, Jordan

AU - Kocak, Mustafa

AU - Bryan, Jordan G.

AU - Humeidi, Ranad

AU - Peck, David

AU - Wu, Xiaoyun

AU - Tang, Andrew A.

AU - Wang, Vickie M.

AU - Bender, Samantha A.

AU - Lemire, Evan

AU - Narayan, Rajiv

AU - Montgomery, Philip

AU - Ben-David, Uri

AU - Garvie, Colin W.

AU - Chen, Yejia

AU - Rees, Matthew G.

AU - Lyons, Nicholas J.

AU - McFarland, James M.

AU - Wong, Bang T.

AU - Wang, Li

AU - Dumont, Nancy

AU - O'Hearn, Patrick J.

AU - Stefan, Eric

AU - Doench, John G.

AU - Harrington, Caitlin N.

AU - Greulich, Heidi

AU - Meyerson, Matthew

AU - Vazquez, Francisca

AU - Subramanian, Aravind

AU - Roth, Jennifer A.

AU - Bittker, Joshua A.

AU - Boehm, Jesse S.

AU - Mader, Christopher C.

AU - Tsherniak, Aviad

AU - Golub, Todd R.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85128052471&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/s43018-019-0018-6

DO - https://doi.org/10.1038/s43018-019-0018-6

M3 - مقالة

C2 - 32613204

SN - 1474-175X

VL - 1

SP - 235

EP - 248

JO - Nature Cancer

JF - Nature Cancer

IS - 2

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this