Figure 1 Metabolic adaptations of cancer cells Figure 1 | Metabolic adaptations of cancer cells. Malignant cancer cells exhibit a high rate of anabolic metabolism, similar to highly proliferative normal cell types. Cancer cells take up large amounts of glucose and glutamine, and use these nutrients to fuel the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS), as well as the pentose phosphate pathway (nucleotide synthesis), and the synthesis of hexosamine (involved in the synthesis of glycosylated molecules), amino acids (proteins), and lipids. Together, these pathways generate sufficient levels of cellular components to support cell proliferation. Malignant cells are also able to take up lactate, free fatty acids, and ketones released predominantly by surrounding catabolic cells, which can be used to replenish TCA-cycle intermediates and to fuel OXPHOS (reverse Warburg effect). Increased generation of reactive oxygen species (ROS) in metabolically active cells necessitates the production of appropriate levels of antioxidants, including the reduced form of glutathione, which is generated by glutathione reductase using the coenzyme NADPH derived from the pentose phosphate pathway. ATP, adenosine triphosphate; BP, bisphosphate (or bisphospho); CoA, coenzyme A; GLUT1/GLUT4, glucose transporter 1/4; MCT1, monocarboxylate transporter 1; MCT4, monocarboxylate transporter 4; NADH, nicotinamide adenine dinucleotide (reduced); NADPH, nicotinamide adenine dinucleotide phosphate (reduced); P, phosphate (or phospho); SLC1A5, solute carrier family 1 member 5 (also known as neutral amino acid transporter B(0)). Martinez-Outschoorn, U. E. et al. (2016) Cancer metabolism: a therapeutic perspective Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2016.60