Mutations in isocitrate dehydrogenase (IDH) are a defining feature for diffuse lower grade gliomas. Small molecule IDH inhibitors have shown reduction of D-2-hydroxyglutarate and improvement in progression free survival. Vorasidenib, a brain penetrant IDH 1 and 2 inhibitor, demonstrated improvement in progression free survival and delayed time to initiation of next line therapy in the phase 3 INDIGO trial which led to its regulatory approval for IDH-mutant grade 2 gliomas. There are active, ongoing trials studying novel IDH inhibitors for recurrent and higher-grade tumors. Additional therapeutic strategies informed by genetic and epigenetic tumor features are undergoing active study.
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Chernet et al. (2025) studied this question.
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