IDH1 mutation

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

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.

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.

This case represents the first report of a BCOR ITD in an IDH-mutant WHO grade 4 astrocytoma. The discovery expands the molecular spectrum of high-grade astrocytomas and highlights the need for further research into the biological, prognostic, and therapeutic significance of BCOR alterations in these tumors.

Co-occurrence of GNAQ, GNAS, and IDH1 mutations may represent a molecular signature of recurrence. Further validation in larger cohorts is needed to define optimal gene panels and VAF thresholds for clinical use.

While targeted agents-such as LSD1 inhibitors, the BCL-2 inhibitor venetoclax, and IDH1 inhibitors-have provided clinical benefit, their efficacy is often limited by compensatory signaling and clonal evolution. This computational study supports the feasibility of a polypharmacology-based strategy for AML therapy by integrating epigenetic modulation, apoptotic reactivation, and metabolic correction within single molecular scaffolds. However, the identified compounds (Belumosudil, DB08512, and Elraglusib) have not yet demonstrated efficacy in AML models; further preclinical validation is warranted to substantiate these predictions and advance translational development.

This may reflect either relaxed positive selection for the mutant IDH1 locus, or negative selection for the hypermethylation phenotype later in tumor evolution. This finding highlights the challenge for therapeutic intervention by mutant IDH1 inhibitors in chondrosarcoma.

However, when combined with immune-stimulatory Ad-TK (adenoviral vectors encoding herpes simplex virus thymidine kinase) and Ad-Flt3L (adenoviral vectors encoding FMS-like tyrosine kinase 3 ligand) gene therapy, CD73 blockade significantly enhanced therapeutic efficacy and increased anti-glioma effector T cell activity. These findings reveal that CD73 inhibition used in combination with immune stimulatory Ad-TK/Ad-Flt3L gene therapy may be an effective treatment for wtIDH1 gliomas, which could be readily translated to the clinical arena.