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Non-oncology drugs are a source of previously unappreciated anti-cancer activity
by
Chen, Yejia
, Bender, Samantha A
, Wang, Li
, Kocak, Mustafa
, Dumont, Nancy
, Golub, Todd R
, Jordan, Rossen
, Tang, Andrew A
, Wu, Xiaoyun
, Narayan, Rajiv
, Vazquez, Francisca
, Ben-David, Uri
, Boehm, Jesse S
, Subramanian, Aravind
, Stefan, Eric
, Peck, David
, Roth, Jennifer A
, Mcfarland, James M
, Greulich, Heidi
, Rees, Matthew G
, O'hearn, Patrick J
, Montgomery, Philip
, Nagari, Rohith T
, Doench, John G
, Bittker, Joshua A
, Spangler, Ryan D
, Humeidi, Ranad
, Meyerson, Matthew
, Bryan, Jordan G
, Corsello, Steven M
, Wong, Bang T
, Tsherniak, Aviad
, Lyons, Nicholas J
, Wang, Vickie M
, Lemire, Evan
, Mader, Christopher C
in
Cancer
/ Cancer Biology
/ Disulfiram
/ Drug dependence
/ Drug resistance
/ Drugs
/ Inflammation
/ Multidrug resistance
/ Oncology
/ Sulfate transporter
/ Sulfates
/ Tumor cell lines
/ Vanadium
2019
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Non-oncology drugs are a source of previously unappreciated anti-cancer activity
by
Chen, Yejia
, Bender, Samantha A
, Wang, Li
, Kocak, Mustafa
, Dumont, Nancy
, Golub, Todd R
, Jordan, Rossen
, Tang, Andrew A
, Wu, Xiaoyun
, Narayan, Rajiv
, Vazquez, Francisca
, Ben-David, Uri
, Boehm, Jesse S
, Subramanian, Aravind
, Stefan, Eric
, Peck, David
, Roth, Jennifer A
, Mcfarland, James M
, Greulich, Heidi
, Rees, Matthew G
, O'hearn, Patrick J
, Montgomery, Philip
, Nagari, Rohith T
, Doench, John G
, Bittker, Joshua A
, Spangler, Ryan D
, Humeidi, Ranad
, Meyerson, Matthew
, Bryan, Jordan G
, Corsello, Steven M
, Wong, Bang T
, Tsherniak, Aviad
, Lyons, Nicholas J
, Wang, Vickie M
, Lemire, Evan
, Mader, Christopher C
in
Cancer
/ Cancer Biology
/ Disulfiram
/ Drug dependence
/ Drug resistance
/ Drugs
/ Inflammation
/ Multidrug resistance
/ Oncology
/ Sulfate transporter
/ Sulfates
/ Tumor cell lines
/ Vanadium
2019
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Do you wish to request the book?
Non-oncology drugs are a source of previously unappreciated anti-cancer activity
by
Chen, Yejia
, Bender, Samantha A
, Wang, Li
, Kocak, Mustafa
, Dumont, Nancy
, Golub, Todd R
, Jordan, Rossen
, Tang, Andrew A
, Wu, Xiaoyun
, Narayan, Rajiv
, Vazquez, Francisca
, Ben-David, Uri
, Boehm, Jesse S
, Subramanian, Aravind
, Stefan, Eric
, Peck, David
, Roth, Jennifer A
, Mcfarland, James M
, Greulich, Heidi
, Rees, Matthew G
, O'hearn, Patrick J
, Montgomery, Philip
, Nagari, Rohith T
, Doench, John G
, Bittker, Joshua A
, Spangler, Ryan D
, Humeidi, Ranad
, Meyerson, Matthew
, Bryan, Jordan G
, Corsello, Steven M
, Wong, Bang T
, Tsherniak, Aviad
, Lyons, Nicholas J
, Wang, Vickie M
, Lemire, Evan
, Mader, Christopher C
in
Cancer
/ Cancer Biology
/ Disulfiram
/ Drug dependence
/ Drug resistance
/ Drugs
/ Inflammation
/ Multidrug resistance
/ Oncology
/ Sulfate transporter
/ Sulfates
/ Tumor cell lines
/ Vanadium
2019
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Non-oncology drugs are a source of previously unappreciated anti-cancer activity
Paper
Non-oncology drugs are a source of previously unappreciated anti-cancer activity
2019
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Overview
Anti-cancer uses of non-oncology drugs have been found on occasion, but such discoveries have been serendipitous and rare. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. To accomplish this, we used PRISM, which involves drug treatment of molecularly barcoded cell lines in pools. Relative barcode abundance following treatment thus reflects viability of each cell line. We found that an unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines. Moreover, the killing activity of the majority of these drugs was predictable based on the molecular features of the cell lines. Follow-up of several of these compounds revealed novel mechanisms. For example, compounds that kill by inducing PDE3A-SLFN12 complex formation; vanadium-containing compounds whose killing is dependent on the sulfate transporter SLC26A2; the alcohol dependence drug disulfiram, which kills cells with low expression of metallothioneins; and the anti-inflammatory drug tepoxalin, whose killing is dependent on high expression of the multi-drug resistance gene ABCB1. These results illustrate the potential of the PRISM drug repurposing resource as a starting point for new oncology therapeutic development. The resource is available at https://depmap.org. Footnotes * https://depmap.org
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
Subject
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