Department of Translational Oncology, Institute of Health Sciences, Dokuz Eylul University.
Student Research Group, Department of Translational Oncology, Institute of Oncology, Dokuz Eylul University.
Anticancer Drugs. 2022 Jan 1;33(1):e69-e75. doi: 10.1097/CAD.0000000000001236.
Energetic pathways combine in the heart of metabolism. These essential routes supply energy for biochemical processes through glycolysis and oxidative phosphorylation. Moreover, they support the synthesis of various biomolecules employed in growth and survival over branching pathways. Yet, cellular energetics are often misguided in cancers as a result of the mutations and altered signaling. As nontransformed and Pasteur-like cells metabolize glucose through oxidative respiration when only oxygen is sufficient, some cancer cells bypass this metabolic switch and run glycolysis at higher rates even in the presence of oxygen. The phenomenon is called aerobic glycolysis or the Warburg effect. An increasing number of studies indicate that both Warburg and Pasteur phenotypes are recognized in the cancer microenvironment and take vital roles in the regulation of drug resistance mechanisms such as redox homeostasis, apoptosis and autophagy. Therefore, the different phenotypes call for different therapeutic approaches. Combined therapies targeting energy metabolism grant new opportunities to overcome the challenges. Nevertheless, new biomarkers emerge to classify the energetic subtypes, thereby the cancer therapy, as our knowledge in coupling energy metabolism with cancer behavior grows.
能量途径在新陈代谢的核心处交汇。这些基本途径通过糖酵解和氧化磷酸化为生化过程提供能量。此外，它们还支持各种生物分子的合成，这些生物分子在生长和存活中通过分支途径发挥作用。然而，由于突变和信号转导的改变，癌细胞中的细胞能量通常会出现误导。当只有氧气充足时，非转化和巴斯德样细胞通过氧化呼吸代谢葡萄糖，而一些癌细胞绕过这种代谢转换，即使在有氧气的情况下，也以更高的速率进行糖酵解。这种现象被称为有氧糖酵解或瓦堡效应。越来越多的研究表明，沃伯格和巴斯德表型都在癌症微环境中得到认可，并在调节药物耐药机制（如氧化还原稳态、细胞凋亡和自噬）方面发挥重要作用。因此，不同的表型需要不同的治疗方法。针对能量代谢的联合治疗为克服这些挑战提供了新的机会。然而，随着我们对能量代谢与癌症行为的了解不断深入，新的生物标志物不断涌现，以对能量亚型进行分类，从而对癌症治疗进行分类。
