Oxidative Phosphorylation as an Emerging Target in Cancer Therapy

Cancer cells have upregulated glycolysis compared with normal cells, which has led many to the assumption that oxidative phosphorylation (OXPHOS) is downregulated in all cancers. However, recent studies have shown that OXPHOS can be also upregulated in certain cancers, including leukemias, lymphomas...

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Bibliographic Details
Published in:Clinical cancer research Vol. 24; no. 11; p. 2482
Main Authors: Ashton, Thomas M, McKenna, W Gillies, Kunz-Schughart, Leoni A, Higgins, Geoff S
Format: Journal Article
Language:English
Published: United States 01.06.2018
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Biomarkers
Energy Metabolism - drug effects
Humans
Metabolic Networks and Pathways
Mitochondria - drug effects
Mitochondria - genetics
Mitochondria - metabolism
Molecular Targeted Therapy - methods
Neoplasms - etiology
Neoplasms - metabolism
Neoplasms - therapy
Oxidative Phosphorylation - drug effects
ISSN:1557-3265, 1557-3265
Online Access:Get more information
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Summary:Cancer cells have upregulated glycolysis compared with normal cells, which has led many to the assumption that oxidative phosphorylation (OXPHOS) is downregulated in all cancers. However, recent studies have shown that OXPHOS can be also upregulated in certain cancers, including leukemias, lymphomas, pancreatic ductal adenocarcinoma, high OXPHOS subtype melanoma, and endometrial carcinoma, and that this can occur even in the face of active glycolysis. OXPHOS inhibitors could therefore be used to target cancer subtypes in which OXPHOS is upregulated and to alleviate therapeutically adverse tumor hypoxia. Several drugs including metformin, atovaquone, and arsenic trioxide are used clinically for non-oncologic indications, but emerging data demonstrate their potential use as OXPHOS inhibitors. We highlight novel applications of OXPHOS inhibitors with a suitable therapeutic index to target cancer cell metabolism. .
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ISSN:1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-17-3070