Although cancer has historically been viewed as a disorder of proliferation, recent evidence has suggested that it should also be considered a metabolic disease. Growing tumors rewire their metabolic programs to meet and even exceed the bioenergetic and biosynthetic demands of continuous cell growth. The metabolic profile observed in cancer cells often includes increased consumption of glucose and glutamine, increased glycolysis, changes in the use of metabolic enzyme isoforms, and increased secretion of lactate.
Why do cancer cells shift their metabolism in this way? Are the changes in metabolism in cancer cells a consequence of the changes in proliferation or a driver of cancer progression? Can cancer metabolism be targeted to benefit patients?
Otto Warburg’s pioneering work in the 1920s established that tumor cells exhibit altered metabolism. Warburg discovered an important distinction between the relative use of different modes of energy production in normal cells and tumors. In normal tissues, most of the pyruvate formed from glycolysis enters the tricarboxylic acid (TCA) cycle and is oxidized via oxidative phosphorylation. In tumors, in contrast, the pyruvate is largely converted to lactic acid and energy is produced anaerobically.