Serine, glycine and one-carbon units: cancer metabolism in full circle

This Review reminds us of all those pathways we longed to forget from first year biochemistry: deregulated one-carbon metabolism is a possible driver of oncogenesis. Given the wealth of clinically available agents that target one-carbon metabolism are there opportunities for translation into precision cancer medicine? One-carbon metabolism involving the folate and methionine cycles integrates nutritional status from amino acids, glucose and vitamins, and generates diverse outputs, such as the biosynthesis of lipids, nucleotides and proteins, the maintenance of redox status and the substrates for methylation reactions. Long considered a 'housekeeping' process, this pathway has recently been shown to have additional complexity. Genetic and functional evidence suggests that hyperactivation of this pathway is a driver of oncogenesis and establishes a link to cellular epigenetic status. Given the wealth of clinically available agents that target one-carbon metabolism, these new findings could present opportunities for translation into precision cancer medicine.