The protein AKT1 (also known as Protein Kinase B or PKB) in the PI3K/AKT/mTOR pathway is an important driver of the tumor glycolytic phenotype and stimulates ATP generation. AKT1 stimulates glycolysis by increasing the expression and membrane translocation of glucose transporters and by phosphorylating key glycolytic enzymes, such as hexokinase and phosphofructokinase 2. This leads to inhibition of forkhead box subfamily O transcription factors, leading to the increase of glycolytic capacity. Activated mTOR stimulates protein and lipid biosynthesis and cell growth in response to sufficient nutrient and energy conditions and is often constitutively activated during tumorigenesis. mTOR directly stimulates mRNA translation and ribosome biogenesis, and indirectly causes other metabolic changes by activating transcription factors such as hypoxia-inducible factor 1 (HIF1A). The subsequent HIF1-dependent metabolic changes are a major determinant of the glycolytic phenotype downstream of PI3K, AKT1 and mTOR.