MGMT promoter methylation

P1, N=56, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting

All patients underwent surgical resection followed by temozolomide-based chemoradiation; two received fotemustine and bevacizumab, and one underwent re-irradiation. EM can arise despite MGMT-promoter methylation in IDH-wildtype GBM. Imaging red flags (high perfusion, surface contact, necrotic/FDG-avid cervical nodes) and clinical cues (axial pain, cytopenias, neck masses) should prompt early systemic staging (CT/PET-CT) and targeted tissue confirmation to advance management.

Rapid vascular recovery is a key feature preceding glioblastoma (GBM) recurrence after radiotherapy (RT). Median progression-free (PFS) and overall survival (OS) after RT + BEV + NOX-A12 were 9.1 and 19.9 months, respectively, significantly outperforming RT + NOX-A12 (p = 0.009; p = 0.021) in a post-hoc comparative analysis, with two patients exceeding 2-year OS. These findings establish proof-of-principle for dual inhibition of CXCL12 and VEGF in patients with newly-diagnosed GBM following RT.

P2, N=30, Active, not recruiting, Cantex Pharmaceuticals | Trial completion date: Jun 2025 --> Dec 2026 | Trial primary completion date: Sep 2024 --> Sep 2026

P2, N=107, Completed, IFOM ETS - The AIRC Institute of Molecular Oncology | Not yet recruiting --> Completed

These findings identify NKCC1 as a regulator of GBM progression and recurrence, linking chloride transporter imbalance to GABAergic signaling. Targeting NKCC1 and restoring chloride homeostasis may provide promising new treatment strategies.

We identified new prognostic markers in GBM, showing for the first time that EGFR substitutions improve OS. Validation in external cohorts and preclinical studies is needed.

We focused on MGMT because MGMT promoter methylation is used as a predictive marker for temozolomide response in GB, but its role in MBM has been discussed controversially...GB exhibited higher methylation, particularly in promoter and intergenic enhancers, and stronger associations between methylation and overall survival than MBM. These results highlight both conserved and tumor-specific MGMT regulation, reflecting the complexity of epigenetic control in brain malignancies and emphasizing divergent evolution between MBM and GB.

P1, N=56, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Feb 2026 --> Feb 2027

P1, N=27, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | Trial completion date: Jan 2030 --> Mar 2029 | Trial primary completion date: Apr 2027 --> Apr 2026

In a predominantly rural state served by a primary academic neuro-oncology program, median overall survival for GBM was 12.7 months indicating centralized care eliminates rural-urban survival gaps in GBM.

The findings challenge current WHO diagnostic criteria regarding H3K27me3 retention and demonstrate the critical role of molecular diagnostics, particularly methylation profiling, in refining classification and guiding clinical management. These results advocate for re-evaluation of existing diagnostic frameworks to better accommodate the observed variability and associations in this challenging tumor subtype.