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Mitochondria are the places for the energy production of the cells, while reactive oxygen species (ROS) are also produced alongside. In recent years, it has been reported that cancer stem cells metabolize predominantly through oxidative phosphorylation (OXPHOS) rather than glycolysis. Targeting OXPHOS achieved by suppression of ATP synthesis through mitochondrial ATP synthase could be a potential therapeutic option against cancer stem cells. Since c-Myc inhibition is considered to lead a metabolic flux to OXPHOS from glycolysis, the combinatory inhibition of both OXPHOS and glycolysis could be a strong candidate for the treatment of malignant tumors. In this chapter, we will discuss about the mitochondria metabolism as the potential therapeutic target in osteosarcoma stem cells, and the synergistic effects of combination of OXPHOS inhibitor with c-Myc inhibitor, which target both OXPHOS-dominant cancer stem cells and glycolysis-dominant non-cancer stem cells, will be discussed.

A Novel Strategy of Dual Inhibition of Distinct Metabolic Features in Osteosarcoma