Figure 1: Metabolic remodeling of cancer cells Schematic highlights key differences in many cancer cells compared to normal tissue.

Normal cells use glycolysis prior to respiration in the mitochondria (yellow) and complete breakdown of glucose by the tricarboxylic acid (TCA) cycle (green). In cancer cells, glycolysis becomes the primary mode of glucose metabolism resulting in lactate and its secretion. The M2 isoform of pyruvate kinase (PKM2) becomes tyrosine phosphorylated and attenuates pyruvate acetyl-CoA conversion while glutaminolysis provides the cancer cell with an alternate source of biosynthetic precursors, fueling the TCA cycle with glutamine-derived a-keto-glutarate. The anti-tumor drug 968 inhibits glutamine metabolism by inhibiting the enzyme glutaminase (GLS).