Abstract

Cancer stem cells (CSCs) play a critical role in tumor initiation, progression, and resistance to therapy. Metabolomics, the comprehensive study of cellular metabolites, has emerged as a powerful tool to uncover the unique metabolic vulnerabilities of CSCs. CSCs exhibit distinct metabolic adaptations, including altered glucose metabolism, lipid synthesis, redox balance, and mitochondrial function, which support their self-renewal and survival under stress conditions. Recent advances in metabolomic profiling have identified key metabolic pathways, such as glycolysis, oxidative phosphorylation, glutamine metabolism, and fatty acid oxidation, that are essential for CSC maintenance and plasticity. Targeting these metabolic dependencies presents a promising therapeutic strategy for eradicating CSCs and overcoming drug resistance. Additionally, metabolic biomarkers hold potential for CSC identification and tracking in cancer progression. Despite these advancements, challenges remain in translating metabolomic insights into clinical applications due to tumor heterogeneity and metabolic plasticity. Future research should focus on integrating metabolomics with multi-omics approaches to develop precision medicine strategies for targeting CSC metabolism.