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Int J Cancer. 2019 Aug 9. doi: 10.1002/ijc.32616. [Epub ahead of print]

Oxidative phosphorylation as a potential therapeutic target for cancer therapy.

Sica V1,2,3, Bravo-San Pedro JM1,2,3, Stoll G1,2,3, Kroemer G1,2,3,4,5,6.

Author information

1
Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.
2
Team "Metabolism, Cancer & Immunity", équipe 11 labellisée par la Ligue contre le Cancer, Paris, France.
3
Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France.
4
Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
5
Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, China.
6
Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

Abstract

In contrast to prior belief, cancer cells require oxidative phosphorylation (OXPHOS) to strive, and exacerbated OXPHOS dependency frequently characterizes cancer stem cells, as well as primary or acquired resistance against chemotherapy or tyrosine kinase inhibitors. A growing arsenal of therapeutic agents is being designed to suppress the transfer of mitochondria from stromal to malignant cells, to interfere with mitochondrial biogenesis, to directly inhibit respiratory chain complexes, or to disrupt mitochondrial function in other ways. For the experimental treatment of cancers, OXPHOS inhibitors can be advantageously combined with tyrosine kinase inhibitors, as well as with other strategies to inhibit glycolysis, thereby causing a lethal energy crisis. Unfortunately, most of the preclinical data arguing in favor of OXPHOS inhibition have been obtained in xenograft models, in which human cancer cells are implanted in immunodeficient mice. Future studies on OXPHOS inhibitors should elaborate optimal treatment schedules and combination regimens that stimulate - or at least are compatible with - anticancer immune responses for long-term tumor control. This article is protected by copyright. All rights reserved.

KEYWORDS:

Warburg phenomenon; bioenergetics; immunotherapy; metabolism; mitochondrial respiration

PMID:
31396957
DOI:
10.1002/ijc.32616

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