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

Contemporary glioma cohorts showed prolonged survival outcomes compared to historical cohorts. An association between anatomic localization and molecular subtypes was also established in this Chinese glioma cohort.

P=N/A, N=63, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: May 2025 --> May 2027

P1, N=27, Recruiting, Washington University School of Medicine | N=12 --> 27

Our findings reveal that R-2HG specifically inhibits microglial inflammatory activation by suppressing the FTO/NF-κB signaling pathway, leading to decreased IL-6 production. This study provides a novel mechanism by which R-2HG modulates the tumor immune microenvironment, which may be beneficial for exploring the basis of antitumor immunity in IDH-mutant gliomas.

Semi-supervised approaches may improve the performance of radiomics-based ML models in predicting glioma IDH1 status. Using pseudolabels, these models can increase the size of training data, potentially leading to enhancement of model predictive performance. Additionally, these models may improve prediction efficiency by requiring fewer image sequences.

To overcome this resistance, we found that treatment with the receptor tyrosine kinase inhibitor, cediranib, previously reported to suppress expression of downstream HDR factors, resensitizes 53BP1 and REV7-knockout cells to PARPi treatment. Our findings identify key pathways driving PARPi resistance in IDH1-mutant cancers and highlight potential therapeutic strategies to overcome this resistance.

This review aims to comprehensively examine the association between IDH1/2 mutations and BBB disruption, elucidating how IDH1/2-mutant gliomas alter tumor-associated metabolic and epigenetic pathways, which subsequently influence microglial activation and polarization, contributing to BBB impairment. Furthermore, we propose that microglia-mediated BBB disruption may be one of the underlying mechanisms contributing to complications in IDH1/2-mutant gliomas, such as vasogenic edema and immune-mediated encephalopathy, both of which are closely associated with BBB breakdown.

Triplet therapies combining hypomethylating agents, venetoclax, and targeted inhibitors are emerging as a promising therapy for older patients with AML unfit for intensive chemotherapy...While effective, the need to remain on indefinite therapy for individuals who are not stem cell transplant candidates and dose optimization/de-escalation strategies remain critical concerns. Herein, we aim to review the current treatment landscape of newly diagnosed and relapsed/refractory FLT3- and IDH1/2-mutated AML and the role of triplet regimens in these molecular subgroups.

New therapeutic options to reduce the red blood cell (RBC) transfusion burden have emerged since 2020 and include luspatercept and imetelstat. Erythropoiesis-stimulating agents and lenalidomide also address anemia and are generally recommended to start at the time of transfusion dependency, although emerging data suggest that an earlier start of these interventions might offer clinical benefits...Targeted therapy directed to the presence of an IDH1 mutation is U.S. Food and Drug Administration (FDA) approved for the rare IDH1 mutated MDS (<10% of the time) and consideration to use an IDH2 inhibitor for IDH2 mutated MDS (<5% of the time) is reasonable. Interestingly, IDH mutations seem to appear with increased frequency in older patients and in patients with underlying autoimmune/rheumatological disorders.1.

OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.

To our knowledge, this is among the first comprehensive reviews to integrate CNS-specific immune privilege mechanisms with peripheral exhaustion pathways, providing a unified perspective on how epigenetic regulation orchestrates immune dysfunction across central and peripheral contexts. By mapping the continuum between immune evasion and global immunosuppression, we propose a conceptual framework for tailoring epigenetic-immunotherapy combinations to achieve durable antitumor immunity in the CNS.