IDH1 R132

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.

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.

P1/2, N=42, Active, not recruiting, Washington University School of Medicine | Trial completion date: Jan 2032 --> Apr 2028

These 5-year data support the durable efficacy and manageable safety profile of olutasidenib in R/R mIDH1 AML, including heavily pretreated patients. Findings highlight the potential role of olutasidenib in earlier lines of treatment, and support sustaining therapy for at least 6 months to allow for a clinical response. Further research is warranted to optimize treatment sequencing and patient selection.

Comparison of IDH and NPM1 trends during follow-up revealed a statistically significant positive correlation, both in raw (β = 0.079, p = 0.001) and ranked data (β = 0.99, p = 0.004), suggesting a co-dynamic pattern potentially useful for surrogate monitoring. While our study cannot yet define the clinical role of IDH mutation assessment by ddPCR due to the lack of comparative follow-up studies, it establishes a solid methodological foundation for standardizing minimal residual disease evaluation via ddPCR, paving the way for future prospective validation.

P3, N=560, Active, not recruiting, CarThera | Recruiting --> Active, not recruiting

P1, N=166, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2026 --> Feb 2027

These compounds demonstrated robust binding affinity and complex stability, suggesting their potential to disrupt the aberrant metabolic pathway to suppress glioma formation. Ultimately, this study underscores the extraordinary potential and innovative strategies of harnessing medicinal plants and their phytochemicals as powerful anticancer agents against glioma.

P2, N=35, Completed, Fabio Iwamoto, MD | Active, not recruiting --> Completed | N=20 --> 35 | Trial completion date: Dec 2026 --> Feb 2025

P2, N=460, Recruiting, Patrick Wen, MD | Trial completion date: Apr 2027 --> Apr 2028 | Trial primary completion date: Feb 2027 --> Feb 2028

This retrospective analysis of the largest single-centre dataset on imaging of HGG in NF-1 patients reported in the literature underscores that it may be more common than previously surmised. The need to look for alarming imaging indicators and raise suspicion in atypical locations like midline structures is essential for early detection and appropriate treatment.

Ivosidenib plus nivolumab was safe with limited clinical benefit. Translational investigation highlights potential of IDH1 inhibition to alter tumor-immune interactions and provides hypotheses for future immune-checkpoint combinations.