In 1931, Otto Warburg demonstrated that cancer cells prioritize high-rate glycolysis over oxidative phosphorylation (OXPHOS), producing large amounts of lactate even when oxygen is abundant. This phenomenon is termed Aerobic Glycolysis.
While OXPHOS yields 36 ATP per glucose versus 2 ATP in glycolysis, fast-dividing cancer cells need carbon skeletons (ribose-5-phosphate, amino acids, lipids) more than max ATP. Rapid glycolytic flux supplies biosynthetic building blocks to sustain accelerated cell proliferation.
Inhibiting GLUT1 or LDHA alone often causes metabolic plasticity shifts back to mitochondrial respiration. Modern oncology explores dual metabolic inhibition (e.g., LDHA blockade + Complex I inhibition) to starve tumors of both energy sources simultaneously.