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Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4

Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name A... Full description

Journal Title: Nature Dec 14, 2017, Vol.552(7684), pp.194-199,199A-199Q
Main Author: Skrott, Zdenek
Other Authors: Mistrik, Martin , Andersen, Klaus , Friis, Søren , Majera, Dusana , Gursky, Jan , Ozdian, Tomas , Bartkova, Jirina , Turi, Zsofia , Moudry, Pavel , Kraus, Marianne , Michalova, Martina , Vaclavkova, Jana , Dzubak, Petr , Vrobel, Ivo , Pouckova, Pavla , Sedlacek, Jindrich , Miklovicova, Andrea , Kutt
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 00280836 ; E-ISSN: 14764687 ; DOI: 10.1038/nature25016
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title: Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
format: Article
creator:
  • Skrott, Zdenek
  • Mistrik, Martin
  • Andersen, Klaus
  • Friis, Søren
  • Majera, Dusana
  • Gursky, Jan
  • Ozdian, Tomas
  • Bartkova, Jirina
  • Turi, Zsofia
  • Moudry, Pavel
  • Kraus, Marianne
  • Michalova, Martina
  • Vaclavkova, Jana
  • Dzubak, Petr
  • Vrobel, Ivo
  • Pouckova, Pavla
  • Sedlacek, Jindrich
  • Miklovicova, Andrea
  • Kutt
subjects:
  • Tumors
  • Copper
  • Epidemiology
  • Cancer
  • Cancer Therapies
  • Mortality
  • Copper Compounds
  • Copper
  • Tumors
  • Chromatography
  • Cancer
  • Proteins
  • Proteins
  • Coordination Compounds
  • Tissues
  • Studies
  • Epidemiology
  • Cancer
  • Anticancer Properties
  • Biomarkers
ispartof: Nature, Dec 14, 2017, Vol.552(7684), pp.194-199,199A-199Q
description: Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing...
language: eng
source:
identifier: ISSN: 00280836 ; E-ISSN: 14764687 ; DOI: 10.1038/nature25016
fulltext: fulltext
issn:
  • 00280836
  • 0028-0836
  • 14764687
  • 1476-4687
url: Link


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titleAlcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
creatorSkrott, Zdenek ; Mistrik, Martin ; Andersen, Klaus ; Friis, Søren ; Majera, Dusana ; Gursky, Jan ; Ozdian, Tomas ; Bartkova, Jirina ; Turi, Zsofia ; Moudry, Pavel ; Kraus, Marianne ; Michalova, Martina ; Vaclavkova, Jana ; Dzubak, Petr ; Vrobel, Ivo ; Pouckova, Pavla ; Sedlacek, Jindrich ; Miklovicova, Andrea ; Kutt
ispartofNature, Dec 14, 2017, Vol.552(7684), pp.194-199,199A-199Q
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subjectTumors ; Copper ; Epidemiology ; Cancer ; Cancer Therapies ; Mortality ; Copper Compounds ; Copper ; Tumors ; Chromatography ; Cancer ; Proteins ; Proteins ; Coordination Compounds ; Tissues ; Studies ; Epidemiology ; Cancer ; Anticancer Properties ; Biomarkers
descriptionCancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing...
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titleAlcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
descriptionCancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing...
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titleAlcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
authorSkrott, Zdenek ; Mistrik, Martin ; Andersen, Klaus ; Friis, Søren ; Majera, Dusana ; Gursky, Jan ; Ozdian, Tomas ; Bartkova, Jirina ; Turi, Zsofia ; Moudry, Pavel ; Kraus, Marianne ; Michalova, Martina ; Vaclavkova, Jana ; Dzubak, Petr ; Vrobel, Ivo ; Pouckova, Pavla ; Sedlacek, Jindrich ; Miklovicova, Andrea ; Kutt
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2Epidemiology
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4Cancer Therapies
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6Copper Compounds
7Chromatography
8Proteins
9Coordination Compounds
10Tissues
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atitleAlcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
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abstractCancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing...
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date2017-12-14