IDH1 R132

IDH1-vac-induced T cell responses were detected in the inflamed brain lesion of an IDH1-vac-associated pseudoprogression, whereas no IDH1-vac-induced T cells were found in participants with early progressive disease. The favorable long-term outcome of the NOA16 cohort supports investigating IDH1-vac in persons with newly diagnosed grade 3 and 4 (World Health Organization classification 2021) IDH-mutant astrocytomas in a randomized phase 2 trial (ClinicalTrials.gov identifier: NCT02454634 ).

P1, N=29, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Treatment was well tolerated and associated with durable radiographic response with tumor reduction, partial metabolic response on FDG-PET imaging, and clinically significant improvement in neurological symptoms and quality of life. This case highlights the value of molecular tumor board-guided interpretation of genomic alterations and illustrates the potential role of IDH-targeted therapy in select patients with recurrent chordoma.

In contrast, miR-340 was downregulated in glioma cells, and its direct transfection markedly inhibited proliferation without astrocyte toxicity; fluorescent miR-340 was also detected within TMs and recipient glioma cells. Together, these findings identify TMs as structural features shaped by IDH1 mutation and as conduits for intercellular exchange of both oncogenic and tumor-suppressive microRNAs, providing a framework for understanding TM-mediated communication and its potential therapeutic exploitation in glioma.

However, elevated expression of poliovirus receptor (PVR) and the immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on tumor-infiltrating leukocytes suggests a potential resistance mechanism to virotherapy. Combining rQNestin34.5 v.2 with TIGIT blockade enhances therapeutic efficacy compared to monotherapy, identifying IDH1-R132H as a potential predictive biomarker for oncolytic virotherapy response.

P3, N=408, Recruiting, Alliance for Clinical Trials in Oncology | Not yet recruiting --> Recruiting | Initiation date: Oct 2025 --> Jul 2026

P1, N=291, Recruiting, Institut de Recherches Internationales Servier | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

P1, N=30, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Jun 2026 --> Dec 2026

Notably, in vitro and in vivo experiments demonstrate that 2-HG induces CDH1 downregulation and reduces quiescent cell populations not only in glioblastoma cells but also in lung cancer and colorectal cancer cells, and consistently sensitizes tumor cells to chemotherapy. Our findings shed light on why IDH1 mutations correlate with better prognosis and highlight the translational potential of 2-HG as a chemotherapy sensitizer.

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.

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.