Milella Martina, Rutigliano Monica, Pandolfo Savio Domenico, Aveta Achille, Crocetto Felice, Ferro Matteo, d'Amati Antonio, Ditonno Pasquale, Lucarelli Giuseppe, Lasorsa Francesco
Urology and Kidney Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area-Urology, University of Bari "Aldo Moro", 70124 Bari, Italy.
Department of Urology, University of L'Aquila, 67100 L'Aquila, Italy.
Cells. 2025 May 15;14(10):717. doi: 10.3390/cells14100717.
Cancer stem cells (CSCs) are a subpopulation with self-renewal and differentiation capacities believed to be responsible for tumor initiation, progression, and recurrence. These cells exhibit unique metabolic features that contribute to their stemness and survival in hostile tumor microenvironments. Like non-stem cancer cells, CSCs primarily rely on glycolysis for ATP production, akin to the Warburg effect. However, CSCs also show increased dependence on alternative metabolic pathways, such as oxidative phosphorylation (OXPHOS) and fatty acid metabolism, which provide necessary energy and building blocks for self-renewal and therapy resistance. The metabolic plasticity of CSCs enables them to adapt to fluctuating nutrient availability and hypoxic conditions within the tumor. Recent studies highlight the importance of these metabolic shifts in maintaining the CSC phenotype and promoting cancer progression. The CSC model suggests that a small, metabolically adaptable subpopulation drives tumor growth and therapy resistance. CSCs can switch between glycolysis and mitochondrial metabolism, enhancing their survival under stress and dormant states. Targeting CSC metabolism offers a promising therapeutic strategy; however, their adaptability complicates eradication. A multi-targeted approach addressing various metabolic pathways is essential for effective CSC elimination, underscoring the need for further research into specific CSC markers and mechanisms that distinguish their metabolism from normal stem cells for successful therapeutic intervention.
癌症干细胞（CSCs）是具有自我更新和分化能力的亚群，被认为与肿瘤的起始、进展和复发有关。这些细胞表现出独特的代谢特征，有助于它们在恶劣的肿瘤微环境中保持干性和存活。与非干细胞样癌细胞一样，癌症干细胞主要依靠糖酵解来产生ATP，类似于瓦伯格效应。然而，癌症干细胞对替代代谢途径的依赖性也增加，如氧化磷酸化（OXPHOS）和脂肪酸代谢，这些途径为自我更新和治疗抗性提供必要的能量和构建模块。癌症干细胞的代谢可塑性使它们能够适应肿瘤内波动的营养可用性和缺氧条件。最近的研究强调了这些代谢转变在维持癌症干细胞表型和促进癌症进展中的重要性。癌症干细胞模型表明，一个小的、具有代谢适应性的亚群驱动肿瘤生长和治疗抗性。癌症干细胞可以在糖酵解和线粒体代谢之间切换，增强它们在应激和休眠状态下的存活能力。靶向癌症干细胞代谢提供了一种有前景的治疗策略；然而，它们的适应性使根除变得复杂。针对各种代谢途径的多靶点方法对于有效消除癌症干细胞至关重要，这突出了进一步研究特定癌症干细胞标志物和区分其与正常干细胞代谢的机制以实现成功治疗干预的必要性。
