Journal article
Emerging evidence for targeting mitochondrial metabolic dysfunction in cancer therapy
The Journal of clinical investigation, Vol.128(9), pp.3682-3691
08/31/2018
DOI: 10.1172/JCI120844
PMCID: PMC6118595
PMID: 30168803
Abstract
Mammalian cells use a complex network of redox-dependent processes necessary to maintain cellular integrity during oxidative metabolism, as well as to protect against and/or adapt to stress. The disruption of these redox-dependent processes, including those in the mitochondria, creates a cellular environment permissive for progression to a malignant phenotype and the development of resistance to commonly used anticancer agents. An extension of this paradigm is that when these mitochondrial functions are altered by the events leading to transformation and ensuing downstream metabolic processes, they can be used as molecular biomarkers or targets in the development of new therapeutic interventions to selectively kill and/or sensitize cancer versus normal cells. In this Review we propose that mitochondrial oxidative metabolism is altered in tumor cells, and the central theme of this dysregulation is electron transport chain activity, folate metabolism, NADH/NADPH metabolism, thiol-mediated detoxification pathways, and redox-active metal ion metabolism. It is proposed that specific subgroups of human malignancies display distinct mitochondrial transformative and/or tumor signatures that may benefit from agents that target these pathways.
Details
- Title: Subtitle
- Emerging evidence for targeting mitochondrial metabolic dysfunction in cancer therapy
- Creators
- Yueming Zhu - Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USAAngela Elizabeth Dean - Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USANobuo Horikoshi - Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USACollin Heer - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, USADouglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, USADavid Gius - Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.128(9), pp.3682-3691
- Publisher
- United States
- DOI
- 10.1172/JCI120844
- PMID
- 30168803
- PMCID
- PMC6118595
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- P30 ES005605 / NIEHS NIH HHS T32 CA078586 / NCI NIH HHS R01 CA168292 / NCI NIH HHS R01 CA182804 / NCI NIH HHS R01 CA152601 / NCI NIH HHS R01 CA214025 / NCI NIH HHS R01 CA152799 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 08/31/2018
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984047774802771
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