Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways

Gaurab Chakrabarti,1,2,4 David E Gerber,3,4 David A Boothman1,2,4 1Department of Pharmacology, 2Department of Radiation Oncology, 3Division of Hematology and Oncology, 4Harold C Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA Abstract: Nicotinamide adenine dinu...

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Autores principales:	Chakrabarti G, Gerber DE, Boothman DA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a3454318a9b045a7b47f2ef216e78196
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spelling	oai:doaj.org-article:a3454318a9b045a7b47f2ef216e781962021-12-02T06:38:01ZExpanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways1179-1438https://doaj.org/article/a3454318a9b045a7b47f2ef216e781962015-03-01T00:00:00Zhttp://www.dovepress.com/expanding-antitumor-therapeutic-windows-by-targeting-cancer-specific-n-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438 Gaurab Chakrabarti,1,2,4 David E Gerber,3,4 David A Boothman1,2,4 1Department of Pharmacology, 2Department of Radiation Oncology, 3Division of Hematology and Oncology, 4Harold C Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA Abstract: Nicotinamide adenine dinucleotide phosphate (NADPH) biogenesis is an essential mechanism by which both normal and cancer cells maintain redox balance. While antitumor approaches to treat cancers through elevated reactive oxygen species (ROS) are not new ideas, depleting specific NADPH-biogenesis pathways that control recovery and repair pathways are novel, viable approaches to enhance cancer therapy. However, to elicit efficacious therapies exploiting NADPH-biogenic pathways, it is crucial to understand and specifically define the roles of NADPH-biogenesis pathways used by cancer cells for survival or recovery from cell stress. It is equally important to select NADPH-biogenic pathways that are expendable or not utilized in normal tissue to avoid unwanted toxicity. Here, we address recent literature that demonstrates specific tumor-selective NADPH-biogenesis pathways that can be exploited using agents that target specific cancer cell pathways normally not utilized in normal cells. Defining NADPH-biogenesis profiles of specific cancer-types should enable novel strategies to exploit these therapeutic windows for increased efficacy against recalcitrant neoplastic disease, such as pancreatic cancers. Accomplishing the goal of using ROS as a weapon against cancer cells will also require agents, such as NQO1 bioactivatable drugs, that selectively induce elevated ROS levels in cancer cells, while normal cells are protected. Keywords: reactive oxygen species (ROS), NQO1-bioactivatable drugs, nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), biogenic pathways, antioxidantChakrabarti GGerber DEBoothman DADove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2015, Iss default, Pp 57-68 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Chakrabarti G Gerber DE Boothman DA Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways
description	Gaurab Chakrabarti,1,2,4 David E Gerber,3,4 David A Boothman1,2,4 1Department of Pharmacology, 2Department of Radiation Oncology, 3Division of Hematology and Oncology, 4Harold C Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA Abstract: Nicotinamide adenine dinucleotide phosphate (NADPH) biogenesis is an essential mechanism by which both normal and cancer cells maintain redox balance. While antitumor approaches to treat cancers through elevated reactive oxygen species (ROS) are not new ideas, depleting specific NADPH-biogenesis pathways that control recovery and repair pathways are novel, viable approaches to enhance cancer therapy. However, to elicit efficacious therapies exploiting NADPH-biogenic pathways, it is crucial to understand and specifically define the roles of NADPH-biogenesis pathways used by cancer cells for survival or recovery from cell stress. It is equally important to select NADPH-biogenic pathways that are expendable or not utilized in normal tissue to avoid unwanted toxicity. Here, we address recent literature that demonstrates specific tumor-selective NADPH-biogenesis pathways that can be exploited using agents that target specific cancer cell pathways normally not utilized in normal cells. Defining NADPH-biogenesis profiles of specific cancer-types should enable novel strategies to exploit these therapeutic windows for increased efficacy against recalcitrant neoplastic disease, such as pancreatic cancers. Accomplishing the goal of using ROS as a weapon against cancer cells will also require agents, such as NQO1 bioactivatable drugs, that selectively induce elevated ROS levels in cancer cells, while normal cells are protected. Keywords: reactive oxygen species (ROS), NQO1-bioactivatable drugs, nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), biogenic pathways, antioxidant
format	article
author	Chakrabarti G Gerber DE Boothman DA
author_facet	Chakrabarti G Gerber DE Boothman DA
author_sort	Chakrabarti G
title	Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways
title_short	Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways
title_full	Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways
title_fullStr	Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways
title_full_unstemmed	Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways
title_sort	expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/a3454318a9b045a7b47f2ef216e78196
work_keys_str_mv	AT chakrabartig expandingantitumortherapeuticwindowsbytargetingcancerspecificnicotinamideadeninedinucleotidephosphatebiogenesispathways AT gerberde expandingantitumortherapeuticwindowsbytargetingcancerspecificnicotinamideadeninedinucleotidephosphatebiogenesispathways AT boothmanda expandingantitumortherapeuticwindowsbytargetingcancerspecificnicotinamideadeninedinucleotidephosphatebiogenesispathways
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Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways

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