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Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent

Nitroglycerin (NTG), a drug that has been in clinical use for more than a century, has a range of actions which make it of particular interest in an oncological setting. It is generally accepted that the main mechanism of action of NTG is via the production of nitric oxide (NO), which improves cardi...

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Autores principales: Sukhatme, Vidula, Bouche, Gauthier, Meheus, Lydie, Sukhatme, Vikas P, Pantziarka, Pan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cancer Intelligence 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583240/
https://www.ncbi.nlm.nih.gov/pubmed/26435741
http://dx.doi.org/10.3332/ecancer.2015.568
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author Sukhatme, Vidula
Bouche, Gauthier
Meheus, Lydie
Sukhatme, Vikas P
Pantziarka, Pan
author_facet Sukhatme, Vidula
Bouche, Gauthier
Meheus, Lydie
Sukhatme, Vikas P
Pantziarka, Pan
author_sort Sukhatme, Vidula
collection PubMed
description Nitroglycerin (NTG), a drug that has been in clinical use for more than a century, has a range of actions which make it of particular interest in an oncological setting. It is generally accepted that the main mechanism of action of NTG is via the production of nitric oxide (NO), which improves cardiac oxygenation via multiple mechanisms including improved blood flow (vasodilation), decreased platelet aggregation, increased erythrocyte O2 release and decreased mitochondrial utilization of oxygen. Its vasoactive properties mean that it has the potential to exploit more fully the enhanced permeability and retention effect in delivering anti-cancer drugs to tumour tissues. Moreover NTG can reduce HIF-1α levels in hypoxic tumour tissues and this may have anti-angiogenic, pro-apoptotic and anti-efflux effects. Additionally NTG may enhance anti-tumour immunity. Pre-clinical and clinical data on these anti-cancer properties of NTG are summarised and discussed. While there is evidence of a positive action as a monotherapy in prostate cancer, there are mixed results in NSCLC where initially positive results have yet to be fully replicated. Based on the evidence presented, a case is made that further exploration of the clinical benefits that may accrue to cancer patients is warranted. Additionally, it is proposed that NTG may synergise with a number of other drugs, including other repurposed drugs, and these are discussed in the supplementary material appended to this paper.
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spelling pubmed-45832402015-10-02 Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent Sukhatme, Vidula Bouche, Gauthier Meheus, Lydie Sukhatme, Vikas P Pantziarka, Pan Ecancermedicalscience Clinical Study Nitroglycerin (NTG), a drug that has been in clinical use for more than a century, has a range of actions which make it of particular interest in an oncological setting. It is generally accepted that the main mechanism of action of NTG is via the production of nitric oxide (NO), which improves cardiac oxygenation via multiple mechanisms including improved blood flow (vasodilation), decreased platelet aggregation, increased erythrocyte O2 release and decreased mitochondrial utilization of oxygen. Its vasoactive properties mean that it has the potential to exploit more fully the enhanced permeability and retention effect in delivering anti-cancer drugs to tumour tissues. Moreover NTG can reduce HIF-1α levels in hypoxic tumour tissues and this may have anti-angiogenic, pro-apoptotic and anti-efflux effects. Additionally NTG may enhance anti-tumour immunity. Pre-clinical and clinical data on these anti-cancer properties of NTG are summarised and discussed. While there is evidence of a positive action as a monotherapy in prostate cancer, there are mixed results in NSCLC where initially positive results have yet to be fully replicated. Based on the evidence presented, a case is made that further exploration of the clinical benefits that may accrue to cancer patients is warranted. Additionally, it is proposed that NTG may synergise with a number of other drugs, including other repurposed drugs, and these are discussed in the supplementary material appended to this paper. Cancer Intelligence 2015-08-27 /pmc/articles/PMC4583240/ /pubmed/26435741 http://dx.doi.org/10.3332/ecancer.2015.568 Text en © the authors; licensee ecancermedicalscience. http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Study
Sukhatme, Vidula
Bouche, Gauthier
Meheus, Lydie
Sukhatme, Vikas P
Pantziarka, Pan
Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent
title Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent
title_full Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent
title_fullStr Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent
title_full_unstemmed Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent
title_short Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent
title_sort repurposing drugs in oncology (redo)—nitroglycerin as an anti-cancer agent
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583240/
https://www.ncbi.nlm.nih.gov/pubmed/26435741
http://dx.doi.org/10.3332/ecancer.2015.568
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