IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

P1, N=30, Recruiting, Servier Bio-Innovation LLC

P1, N=160, Recruiting, SystImmune Inc. | N=120 --> 160

In this study, we demonstrate that IDH1-mutant AML cells are markedly more sensitive to cuproptosis induced by the copper ionophore elesclomol (ES), compared to their wild-type counterparts...In vivo experiments confirm that ES more effectively suppresses tumor growth in IDH1-mutant xenografts. These findings uncover a copper-dependent metabolic vulnerability and provide a rationale for exploiting cuproptosis as a therapeutic strategy in IDH1-mutant AML.

Rare gain-of-function variants in IDH1/IDH2 are associated with increased risk of immune-mediated rheumatic diseases, particularly rheumatoid arthritis and polymyalgia rheumatica.

Key metabolic alterations, including increased levels of the known biomarker 2-hydroxyglutaric acid, were detected in IDH1-mutant cells compared with wild-type cells. These findings establish hydrogen gas-based GC/MS with a hydrogen-deactivated ion source as a robust and reliable platform for metabolomics, offering an effective alternative to helium-based systems.

Therapeutic advances are highlighted, with particular emphasis on brain-penetrant IDH inhibition (vorasidenib) and on emerging strategies including vaccines, checkpoint combinations, epigenetic modulation, metabolic and microenvironment targeting, and novel delivery platforms...Finally, future directions in trial design, survivorship-oriented endpoints, and biomarker-driven monitoring are outlined. A trajectory-based paradigm is emphasized in which neurocognitive preservation, time to radiotherapy or chemotherapy, and patient-reported outcomes are prioritized while durable disease control is pursued across decades-long survivorship.

These mechanistic effects translated into a survival benefit in oligodendroglioma xenograft-bearing mice. Together, these findings suggest that IDH1-mutant oligodendroglioma harbors a pre-existing heightened sensitivity to ceramide stress and identify acid ceramidase as a therapeutically actionable target in this disease.

P2, N=50, Not yet recruiting, PETHEMA Foundation

A 7-T susceptibility-weighted MRI-based intratumoral susceptibility signal (ITSS) grading system enables precise detection of glioma microbleeds and neovascularization. 7-T susceptibility-weighted MRI-derived ITSS grade noninvasively predicts histologic grade, Ki-67 labeling index, and telomerase reverse transcriptase (TERT) promoter mutation status in gliomas. Path analysis suggested that molecular markers relate to ITSS grade through distinct pathways, with Ki-67 and TERT exerting direct effects and isocitrate dehydrogenase 1 influencing ITSS grade indirectly.

P2, N=35, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

The data demonstrate how molecular glioma characteristics affect peritumoral neuronal circuits. Modulating interactions at the BTI might pave the way for novel therapies.

IDH1 mutations and their associated oncometabolite D-2HG remodel the innate lymphoid cell landscape in gliomas, driving an ILC3-biased phenotype with reduced checkpoint receptor expression. These findings identify ILCs as key modulators of glioma immunity and suggest that targeting innate immune pathways could complement existing immunotherapeutic approaches.