IDH1 mutation

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.

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.

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.

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.

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.

Current first-line therapy for advanced IDH1-mutant disease includes gemcitabine plus cisplatin combined with either durvalumab or pembrolizumab. Ivosidenib is commonly used as a second-line targeted therapy...More prospective clinical trials are needed to validate ctDNA-guided risk stratification, support treatment decisions on adjuvant therapy escalation or de-escalation, and enable treatment adaptation in IDH-mutant CCA, ultimately advancing precision oncology beyond the capabilities of imaging alone. This review aims to evaluate the potential of ctDNA-based MRD detection to refine precision treatment strategies in IDH-mutant CCA.

We investigated the effects of short-term (5 days) and long-term (≥5 weeks) exposure to the IDH1 inhibitor AGI-5198 on radiation-induced cytotoxicity...Effects were comparable to short-term treatment, while radiation responses varied by genetic context. No deleterious interaction between IDHi and IR was observed in endogenous IDH-mutant cells except for MGG18 Tet+ supporting integration of IDHi with radiotherapy in IDH mutant gliomas.

IDH2 and TP53 mutations are enriched in dedifferentiated CS and are significant, independent predictors of adverse survival, regardless of tumor grade. These findings support IDH2 mutation status as clinically meaningful prognostic biomarker that may allow risk stratification and clinical decision-making in CS patients.

P1, N=18, Recruiting, Memorial Sloan Kettering Cancer Center | N=36 --> 18

While no significant synergistic effects were observed in survival endpoints, differences emerged at the level of early DNA damage effects, with IDH1-mutant glioma cells displaying an enhanced acute response following combined treatment with proton irradiation. These findings support further pharmacological development of boron-based SRC-targeted strategies and underscore the importance of tailoring therapeutic approaches to specific glioma molecular subtypes.