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Updated: Aug 4, 2025
Assessment of the Metabolic Profile of Primary Leukemia Cells
Published on: November 21, 2018
OXPHOS inhibitors, metabolism and targeted therapies in cancer
Octavia Cadassou1, Lars Petter Jordheim1
1Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France.
Abstract:
More and more studies highlight the complex metabolic characteristics and plasticity of cancer cells. To address these specificities and explore the associated vulnerabilities, new metabolism-targeting therapeutic strategies are being developed. It is more and more accepted that cancer cells do not produce their energy only from aerobic glycolysis, as some subtypes strongly rely on mitochondrial respiration (OXPHOS). This review focuses on classical and promising OXPHOS inhibitors (OXPHOSi), unravelling their interest and modes of actions in cancer, particularly in combination with other strategies. Indeed, in monotherapy, OXPHOSi display limited efficiency as they mostly trigger cell death in cancer cell subtypes that strongly depend on mitochondrial respiration and are not able to shift to other metabolic pathways to produce energy. Nevertheless, they remain very interesting in combination with conventional therapeutic strategies such as chemotherapy and radiotherapy, increasing their anti-tumoral actions. In addition, OXPHOSi can be included in even more innovative strategies such as combinations with other metabolic drugs or immunotherapies.
Insights
Cancer cells exhibit complex metabolism, relying on mitochondrial respiration (OXPHOS). OXPHOS inhibitors show promise, especially when combined with other cancer therapies for enhanced anti-tumoral effects.
Area of Science:
- Oncology
- Cancer Metabolism
- Mitochondrial Respiration
Background:
- Cancer cells display metabolic plasticity and unique metabolic characteristics.
- While aerobic glycolysis is recognized, some cancer subtypes heavily depend on mitochondrial respiration (OXPHOS) for energy.
- This highlights the need for targeted metabolic therapies.
Purpose of the Study:
- To review classical and novel OXPHOS inhibitors (OXPHOSi) for cancer treatment.
- To explore the mechanisms of action of OXPHOSi.
- To investigate the potential of OXPHOSi in combination therapies.
Main Methods:
- Literature review of existing studies on OXPHOS inhibitors in cancer.
- Analysis of the efficacy of OXPHOSi in monotherapy versus combination therapy.
- Exploration of different therapeutic combinations involving OXPHOSi.
Main Results:
- OXPHOSi demonstrate limited efficacy as monotherapy, primarily affecting cancer cells highly dependent on OXPHOS.
- These cells often lack the ability to switch metabolic pathways for energy production.
- Combinations of OXPHOSi with chemotherapy and radiotherapy enhance anti-tumoral activity.
Conclusions:
- OXPHOS inhibitors are valuable in combination strategies for cancer treatment.
- Innovative combinations include other metabolic drugs or immunotherapies.
- Targeting OXPHOS offers a promising avenue for developing novel cancer therapeutics.
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