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• W2766297389 abstract "Mutations in IDH1 are highly prevalent in human glioma. First line treatment is radiotherapy, which many patients often forego to avoid treatment-associated morbidities. The high prevalence of IDH1 mutations in glioma highlights the need for brain-penetrant IDH1 mutant-selective inhibitors as an alternative therapeutic option. Here, we have explored the utility of such an inhibitor in IDH1 mutant patient-derived models to assess the potential therapeutic benefits associated with intracranial 2-HG inhibition. Treatment of mutant IDH1 cell line models led to a decrease in intracellular 2-HG levels both in vitro and in vivo. Interestingly, inhibition of 2-HG production had no effect on in vitro IDH1 mutant glioma cell proliferation. In contrast, IDH1 mutant-selective inhibitors provided considerable survival benefit in vivo. However, even with near complete inhibition of intratumoral 2-HG production, not all mutant glioma models responded to treatment. The results suggest that disruption of 2-HG production with brain-penetrant inhibitors in IDH1 mutant gliomas may have substantial patient benefit." @default.
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• W2766297389 date "2017-10-23" @default.
• W2766297389 modified "2023-09-30" @default.
• W2766297389 title "A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit" @default.
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• W2766297389 doi "https://doi.org/10.1038/s41598-017-14065-w" @default.
• W2766297389 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5653818" @default.
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