Taking the view that alteration of intracellular signaling through the PI3K pathway is deemed crucial to achieve a cancer metabolic phenotype through the Warburg effect, our study highlights the previously unreported observation that pathway-specific inhibitors targeting either PI3K/mTOR or Akt counteract lactate production to an extent similar to that obtained by 2-DG, as indicated by the shift of the ECAR. This evidence concerns the gene AKT1 and cancer.