越来越多的研究凸显出癌细胞的复杂代谢特征和可塑性。为了应对这些特异性和探索相关的脆弱性，正在开发新的代谢靶向治疗策略。越来越多的人认为，癌细胞不仅仅通过有氧糖酵解产生能量，某些亚型强烈依赖于线粒体呼吸（OXPHOS）。本综述重点介绍了经典和有前途的OXPHOS抑制剂（OXPHOSi），揭示了它们在癌症中的兴趣和作用方式，特别是与其他策略结合使用。确实，在单药治疗中，OXPHOSi的效率有限，因为它们主要触发对线粒体呼吸强烈依赖并不能转向其他代谢途径产生能量的癌细胞亚型的细胞死亡。然而，它们在与传统的治疗策略如化疗和放疗结合使用时仍然非常有趣，增强了它们的抗肿瘤作用。此外，OXPHOSi可以包含在更具创新性的策略中，例如与其他代谢药物或免疫治疗的联合使用。Copyright © 2023 Elsevier Inc. All rights reserved.

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.Copyright © 2023 Elsevier Inc. All rights reserved.