mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability (Cancer Cell)

mTORC1 drives anabolic tumor metabolism, including ribosome biogenesis and nucleotide synthesis. Valvezan et al. show that blocking synthesis of guanine nucleotides while sustaining mTORC1 activity depletes nucleotide pools, causing DNA replication stress and apoptosis in mTORC1-driven tumor models.