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Figure 1. mTORC2 is a kingpin of the Warburg effect and drug resistance. mTORC2 inhibits FoxO via acetylation, whereas PI3K/Akt via phosphorylation, leading to the upregulation of c-Myc, a key effector of the Warburg effect. PI3K/Akt-targeted therapies alone can be bypassed by mTORC2-mediated pathways, whereas targeting both PI3K/Akt and mTORC2 potently suppresses c-Myc and the Warburg effect.
