Serine and one-carbon metabolism in cancer

Serine supports many biosynthetic pathways, including the one-carbon cycle. This Review discusses how cancer cells acquire and use serine, and explores novel therapeutic approaches to limit serine metabolism. The non-essential amino acid serine supports several metabolic processes that are crucial for the growth and survival of proliferating cells, including protein, amino acid and glutathione synthesis. As an important one-carbon donor to the folate cycle, serine contributes to nucleotide synthesis, methylation reactions and the generation of NADPH for antioxidant defence. Many cancer cells are highly dependent on serine, a trait that provides several novel therapeutic opportunities, either through the inhibition of de novo serine synthesis or by limiting the availability or uptake of exogenous serine.