Glutamine antagonism suppresses tumor growth in adrenocortical carcinoma through inhibition of de novo nucleotide biosynthesis.

ABSTRACT: Dysregulation of cellular metabolism is a hallmark of cancer, which remains poorly understood in adrenocortical carcinoma (ACC). Here, we dissected ACC metabolism by integrating transcriptional profiling from human and mouse ACC, targeted tissue metabolomics from a mouse ACC model, and untargeted serum metabolomics from a large patient cohort, providing cross-species validation of metabolic rewiring in ACC. This study revealed global metabolic dysregulation, involving glutamine-dependent pathways such as non-essential amino-acid and hexosamine biosynthesis, nucleotide metabolism, and glutathione biosynthesis, suggesting glutamine catabolism is a critical metabolic vulnerability in ACC. Treatment with glutamine antagonists 6-Diazo-5-Oxo-L-Norleucine (DON) and JHU-083 elicited robust anti-tu

SUBMITTER: Chortis V 

PROVIDER: S-EPMC12621870 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature