IDH1 mutation

Adding ivosidenib to gemcitabine and cisplatin in this study demonstrated a challenging safety profile in advanced CCA. Further research and dose optimization are warranted to confirm these findings and optimize the integration of targeted therapies into first-line regimens.

Metabolomic analyses further demonstrated a significant reduction in asparagine in A1074, consistent with the activation of L-asparaginase-mediated pathways. Collectively, these findings indicate that sustained DS-1001b administration exerts antitumor effects in IDH1-mutant glioma mouse models and induces transcriptomic, epigenetic, and metabolic reprogramming.

In addition, treatments with the IDH-mutant inhibitors vorasidenib and ivosidenib further sensitize the cells to ferroptosis. Furthermore, dietary cysteine-methionine deprivation alone or in combination with convection-enhanced delivery of RSL3 or ivosidenib in vivo significantly prolongs survival of IDH1-mutant tumor-bearing mice. Our findings suggest that targeting cysteine and methionine metabolism in combination with IDH-mutant inhibition provides promising therapeutic strategies for IDH1-mutant gliomas.

P1/2, N=29, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

The new prognostic scale for overall survival, based on molecular data, allows not only to predict further course of disease, but also to recommend irradiation 3 Gy for patients in classes 1-3 as an alternative to radiotherapy.

This study constructed and validated a metabolism-driven prognostic model. The model enables prognostic stratification of LGG patients and links high-risk scores to metabolic dysregulation and an immunosuppressive microenvironment characterized by M2 macrophage enrichment, based on multi-omics data. Mechanistic exploration indicates this association is particularly pronounced in myeloid cells, predominantly within metabolism-related M2 macrophage subpopulations. Furthermore, computational analysis suggests differences in drug sensitivity between risk groups and identifies potential therapeutic compounds, providing clues for future exploration of therapeutic strategies targeting metabolic-immune interactions.

Inhibitors of mutated IDH1 and IDH2, vorasidenib, ivosidenib, olutasidenib, and enasidenib, respectively, were recently approved by the FDA for relapsed/refractory AML. In this review, we mainly focus on IDH inhibitors in leukemia therapy, including the discovery, structure optimization, activity of IDH inhibitors, and applications, which provided the reference for the discovery of new anticancer agents.

P1, N=15, Recruiting, Virginia Commonwealth University | Not yet recruiting --> Recruiting | Trial completion date: Oct 2029 --> Oct 2030 | Trial primary completion date: Oct 2027 --> Oct 2028

These findings highlight the therapeutic potential of targeting the MIF-CD74 pathway and underscore the importance of integrating immunomodulatory strategies for the treatment of glioma. Mutant IDH1 gliomas exhibit fewer Mo-TAMs and increased Mg-TAMsMutant IDH1 gliomas have less MIF expression via epigenetic reprogramming.Mesenchymal wtIDH1 glioma cells are main source of MIF.MIF inhibition plus immune stimulatory gene therapy extends survival wtIDH1 glioma.

Similarly, the random weights analysis favored ivosidenib with all evaluated weights and results converging quickly towards the main analysis results. These results provide comprehensive evidence that ivosidenib is an effective treatment with a tolerable safety profile for this aggressive disease, supporting previous data (ClinicalTrials.gov NCT02989857).

P2, N=55, Recruiting, Stephen Bagley, MD, MSCE | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2027

At the network level, physiological PPIs exhibit high shared ncRNA buffering capacity, whereas oncogenic interactions are characterized by reduced or absent RNA overlap. AlphaFold3 modelling of mutant IDH1/2 complexes illustrates how loss of RNA buffering permits excessive stabilization of enzyme-associated interfaces, reflected by directional changes in buried surface area (ΔBSA) and contact heterogeneity.