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The Metabolic Landscape of Cancer Stem Cells: Insights and Implications for Therapy

Martina MilellaUrology and Kidney Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area-Urology, University of Bari “Aldo Moro”, 70124 Bari, ItalyMonica RutiglianoUrology and Kidney Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area-Urology, University of Bari “Aldo Moro”, 70124 Bari, ItalySavio Domenico PandolfoDepartment of Neurosciences, Science of Reproduction and Odontostomatology, Federico II University, 80138 Naples, ItalyAchille AvetaDepartment of Urology, University of L’Aquila, 67100 L’Aquila, ItalyFelice CrocettoDepartment of Urology, University of L’Aquila, 67100 L’Aquila, ItalyMatteo FerroUrology Unit, Department of Health Science, University of Milan, 20122 Milan, ItalyAntonio d’AmatiUrology and Kidney Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area-Urology, University of Bari “Aldo Moro”, 70124 Bari, ItalyPasquale DitonnoUrology and Kidney Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area-Urology, University of Bari “Aldo Moro”, 70124 Bari, ItalyGiuseppe LucarelliSSD Urologia Clinicizzata, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyFrancesco LasorsaUrology and Kidney Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area-Urology, University of Bari “Aldo Moro”, 70124 Bari, Italy
2025en
ABI

Аннотация

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.

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