The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

SIMPLE SUMMARY: Cancer stem cells (CSCs) have been shown to be the main cause of therapy resistance and cancer recurrence. An analysis of their biological properties has revealed that CSCs have a particular metabolism that differs from non-CSCs to maintain their stemness properties. In this review, we analyze the flexible metabolic mechanisms of CSCs and highlight the new therapeutics that target CSC metabolism. ABSTRACT: Numerous findings have indicated that CSCs, which are present at a low frequency inside primary tumors, are the main cause of therapy resistance and cancer recurrence. Although various therapeutic methods targeting CSCs have been attempted for eliminating cancer cells completely, the complicated characteristics of CSCs have hampered such attempts. In analyzing the biological properties of CSCs, it was revealed that CSCs have a peculiar metabolism that is distinct from non-CSCs to maintain their stemness properties. The CSC metabolism involves not only the catabolic and anabolic pathways, but also intracellular signaling, gene expression, and redox balance. In addition, CSCs can reprogram their metabolism to flexibly respond to environmental changes. In this review, we focus on the flexible metabolic mechanisms of CSCs, and highlight the new therapeutics that target CSC metabolism.