Fig. 6

Metabolic plasticity of CSCs and tumor-specific metabolic adaptations. a Cancer stem cells adapt their metabolism on the basis of nutrient and oxygen availability: basal-like breast CSCs predominantly rely on glycolysis (nutrient-rich, hypoxic conditions), colorectal CSCs utilize a hybrid glycolytic/OXPHOS phenotype, and glioma or luminal breast CSCs primarily employ OXPHOS (nutrient-poor, oxygen-rich environments). This metabolic flexibility supports CSC survival and therapy resistance. b Glutamine metabolism supports CSC proliferation and redox homeostasis. Pancreatic CSCs are strongly dependent on glutamine metabolism and utilize glutamate and aspartate as key intermediates to fuel the TCA cycle and sustain nucleotide biosynthesis under nutrient-limited conditions. Additionally, glutamine metabolism contributes to redox balance, as the conversion of glutamine-derived α-KG to OAA supports NADPH generation via malate metabolism, which maintains the GSH/GSSG cycle to mitigate oxidative stress. Created with BioRender.com