IDH1 R132

Compared to supratentorial tumors, non-R132H IDH1 mutations are significantly more frequent in infratentorial tumors. IDH2-mutant gliomas almost exclusively occur in adults and in supratentorial locations, with a significantly higher proportion in oligodendrogliomas than astrocytoma.

Integrated pathologic-molecular analysis is essential for accurately classifying supratentorial papillary glioneuronal tumors. Classic PGNTs are molecularly defined by recurrent PRKCA fusions, while BRAF-altered cases warrant reclassification.

P1, N=24, Not yet recruiting, Megan Mantica

P3, N=57, Active, not recruiting, Servier | Trial primary completion date: Oct 2025 --> May 2026

Oligo Cdkn2a tumors displayed metabolic and transcriptional changes associated with IDH and CIC mutations, and single cell sequencing identified a bias towards oligodendrocyte differentiation compared to an IDH wild-type glioblastoma mouse model. Oligo Cdkn2a tumors represent the first mouse model system to recapitulate the genetic, histological and transcriptional features of human IDH-mutant 1p/19q-codeleted oligodendrogliomas, offering a platform to further dissect tumor biology and test new therapeutic strategies.

P1, N=2, Terminated, Northwestern University | Active, not recruiting --> Terminated; Low accrual

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.

These preliminary data might indicate that targeted therapies should be introduced in first line with different strategies depending on molecular alterations, with access to platinum-based palliative systemic anti-cancer treatment being important for patients with IDH1-mutated BTC.

Advanced tools such as genome-wide methylation profiling or metabolic imaging may add value in specialized centers. The consensus-based "Golden Rules" pragmatically support harmonization of diagnostic workflows, reducing technical costs and turnaround time, and promoting equitable access to IDH-directed therapies across diverse healthcare settings.

These findings demonstrate that mutant IDH1 promotes KRAS-associated transcriptional programs, at least in part, through epigenetic mechanisms involving H3K36 methylation-dependent chromatin regulation in glioma.

P3, N=265, Active, not recruiting, NRG Oncology | Trial primary completion date: Aug 2026 --> Feb 2026

IDH1 mutations were associated with global transcriptional repression and evidence of metabolic and epigenetic reprogramming. These results depict IDH-mutant prostate cancer as a subtype that can present with high tumor stage and grade, but is associated with favorable outcomes.