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Postoperative risk of IDH mutant glioma-associated seizures and their potential management with IDH mutant inhibitors

ABSTRACT: Postoperative risk of IDH mutant glioma-associated seizures and their potential management with IDH mutant inhibitors

PROVIDER: PRJNA947636 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23942848.fastq.gz	Fastqsanger.gz
	SRR23942849.fastq.gz	Fastqsanger.gz
	SRR23942850.fastq.gz	Fastqsanger.gz
	SRR23942851.fastq.gz	Fastqsanger.gz
	SRR23942852.fastq.gz	Fastqsanger.gz

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Postoperative risk of IDH mutant glioma-associated seizures and their potential management with IDH mutant inhibitors

Project description:To investigate the peri-tumoral effect of IDHmut vs IDHwt glioma, we engrafted IDHmut or IDHwt mouse glioma intracranially in C57BL/6 mice.

2024-04-21 | GSE227995 | GEO

Postoperative risk of IDH-mutant glioma-associated seizures and their potential management with IDH-mutant inhibitors.

Project description:Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.

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Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma I

Project description:Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma I

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Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma III

Project description:Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma III

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Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma II

Project description:Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma II

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Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis

Project description:This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled brain metastasis. The study will have three phases, Phase 1, Phase 2a and Phase 2b.

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Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma II

Project description:A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation towards the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.

2024-05-01 | GSE260933 | GEO

Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma III

2024-05-01 | GSE260997 | GEO

Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma I

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Mutant IDH modulates suppressive myeloid populations in malignant glioma

Project description:RNA-sequencing for myeloid inflammation-related genes was conducted on primary tumor samples from patients with IDH-wildtype glioblastoma (GBM) and grade 4 IDH-mutant astrocytoma (G4IMA). In addition, the IDH-wildtype murine glioma cell line GL261 and a strain of IDH-mutant GL261 were also sequenced using the murine counterpart of the RNA-sequencing myeloid innate immunity panel.

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