Faculty of Medicine, Institute for Applied Molecular Medicine (IMMA), CEU San Pablo University, 28668, Madrid, Spain.
Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Madrid, Spain; Brain Tumor Laboratory, Fundación Vithas, Grupo Hospitales Vithas, 28043, Madrid, Spain.
Mol Metab. 2021 Dec;54:101389. doi: 10.1016/j.molmet.2021.101389. Epub 2021 Nov 5.
Aberrant metabolism is recognized as a hallmark of cancer, a pillar necessary for cellular proliferation. Regarding bioenergetics (ATP generation), most cancers display a preference not only toward aerobic glycolysis ("Warburg effect") and glutaminolysis (mitochondrial substrate level-phosphorylation) but also toward other metabolites such as lactate, pyruvate, and fat-derived sources. These secondary metabolites can assist in proliferation but cannot fully cover ATP demands.
The concept of a static metabolic profile is challenged by instances of heterogeneity and flexibility to meet fuel/anaplerotic demands. Although metabolic therapies are a promising tool to improve therapeutic outcomes, either via pharmacological targets or press-pulse interventions, metabolic plasticity is rarely considered. Lack of bioenergetic analysis in vitro and patient-derived models is hindering translational potential. Here, we review the bioenergetics of cancer and propose a simple analysis of major metabolic pathways, encompassing both affordable and advanced techniques. A comprehensive compendium of Seahorse XF bioenergetic measurements is presented for the first time.
Standardization of principal readouts might help researchers to collect a complete metabolic picture of cancer using the most appropriate methods depending on the sample of interest.
代谢异常被认为是癌症的一个标志，是细胞增殖所必需的支柱。关于生物能量学（ATP 生成），大多数癌症不仅表现出对有氧糖酵解（“Warburg 效应”）和谷氨酰胺分解（线粒体底物水平磷酸化）的偏好，还表现出对其他代谢物如乳酸盐、丙酮酸和脂肪衍生来源的偏好。这些次生代谢物可以协助增殖，但不能完全满足 ATP 的需求。
静态代谢谱的概念受到异质性和灵活性的挑战，以满足燃料/补料需求。尽管代谢疗法是一种很有前途的改善治疗效果的工具，无论是通过药理靶点还是压力脉冲干预，但代谢可塑性很少被考虑。缺乏体外和患者来源模型的生物能量分析阻碍了转化潜力。在这里，我们回顾了癌症的生物能量学，并提出了一种对主要代谢途径的简单分析，包括经济实惠和先进的技术。首次提出了 Seahorse XF 生物能量学测量的综合纲要。
主要读数的标准化可能有助于研究人员根据感兴趣的样本，使用最合适的方法收集癌症的完整代谢图谱。
