Enzyme

Biology

Gene

IDH1

Mutant

Pyrimidine metabolism

Purine

Isocitrate dehydrogenase

Dihydroorotate dehydrogenase

Glioma

Cancer research

Biochemistry

Cancer Cell

Shi et al. show that IDH-mutant gliomas are hyperdependent on de novo pyrimidine nucleotide synthesis. Using a newly developed, genetically engineered mouse model of IDH mutant glioma and patient-derived models, they show that blocking pyrimidine synthesis with the DHODH inhibitor BAY 2402234 is effective against these tumors.

De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma