IDH1 mutation

Unlike HCC, roughly 45% of iCCA harbor alterations amenable to precision oncology approaches, including fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, ERBB2 alterations, and BRAF mutations. In this review, we explore how this framework has reshaped liver cancer care and discuss the resulting breakthroughs in management and emerging directions that may further improve therapeutic strategies.

We characterized the distribution of IDH1 mutations in a large cohort of patients with ICC from China. The presence of IDH1 mutations was associated with better survival and decreased risk of recurrence in patients with resected ICC that received adjuvant chemotherapy.

We report a rare case of dedifferentiated chondrosarcoma of the cavernous sinus in a specimen containing only the dedifferentiated component and exhibiting an IDH1 mutation, underscoring the importance of genetic characterization for the differential diagnosis of tumors in this anatomical region. Given the recent evidence supporting the efficacy of IDH inhibitors in chondrosarcomas, identifying mutations in these genes may also have significant therapeutic implications.

We report the first case of a patient with OD in whom PHPT was diagnosed and associated with the presence of an IDH1 mutation detected in a parathyroid adenoma. This observation suggests a possible role of IDH1 mutations in parathyroid tumorigenesis in OD and underscores the need to consider endocrine manifestations in this condition.

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.