Oxidative phosphorylation as a potential therapeutic target for cancer therapy |
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Authors: | Valentina Sica José Manuel Bravo-San Pedro Gautier Stoll Guido Kroemer |
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Affiliation: | 1. Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France;2. Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France Team “Metabolism, Cancer & Immunity”, équipe 11 labellisée par la Ligue contre le Cancer, Paris, France Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France |
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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. |
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Keywords: | bioenergetics immunotherapy metabolism mitochondrial respiration Warburg phenomenon |
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