2025/04/19 by Suresh Udutha, Céline Taglang, Georgios Batsios +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Epigenetics and DNA Methylation #Cancer-related Molecular Pathways #Cancer, Hypoxia, and Metabolism
paper · doi:10.1016/j.celrep.2025.115596
openalex publication_date 2025/04/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
C]-glutamine in GBMs. However, GCLC inhibition drives de novo pyrimidine nucleotide biosynthesis by upregulating the glutamine-utilizing enzymes glutaminase (GLS) and carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotatase (CAD) in an MYC-driven manner. Combining BSO with the glutamine antagonist JHU-083 is synthetically lethal in vitro and in vivo and significantly extends the survival of mice bearing intracranial GBM xenografts. Collectively, our studies advance our understanding of oncogene-induced metabolic vulnerabilities in GBMs.