MGMT promoter methylation

P3, N=306, Suspended, NRG Oncology | Recruiting --> Suspended

Drug sensitivity analyses suggested that high-risk GBM may respond better to paclitaxel and tamoxifen. Random Forest modeling and in vitro experiments identified GJB2 as an oncogenic driver that promotes GBM cell proliferation and migration. Our findings provide a clinically applicable EMT-based prognostic framework that links transcriptional plasticity to patient outcomes in GBM and identify GJB2 as a promising therapeutic target.

Contrary to prior literature, we observed no significant hemispheric preference regarding MGMT promoter methylation status. Our findings challenge prior assumptions regarding the spatial distinctiveness of GB subtypes and highlight the need to further elucidate the mechanisms governing tumorigenesis and spatial growth patterns.

RANO Class 1 resection and a Karnofsky Performance Status ≥ 70 at recurrence appear to be key prdictors to improved post-recurrence survival and preserving quality of life in rGBM patients. Additional factors, including tumor volume at recurrence, ependymal involvement, and MGMT promoter methylation status, should be carefully integrated into the multidisciplinary assessment of suitability for reopration in rGBM patients.

Recurrent alterations included NF1 (87.5%), PTEN (62.5%), and TERT promoter mutations (25%), with a single BRAF V600E-mutant tumor, while the classical +7/ - 10 signature was infrequent and MGMT promoter methylation was largely absent in GBM, IDH-wildtype. This study demonstrates that a substantial subset of pediatric and AYA HGGs harbor molecularly adult-type signatures, revealing the limitations of conventional histopathology and immunohistochemistry, challenging age-based diagnostic paradigms, and highlights the value of methylation profiling for diagnostic refinement, detection of targetable alterations in younger patients.

The framework supports real-world applicability in heterogeneous imaging environments. Future work should focus on external validation and integration with clinical and molecular biomarkers to further enhance predictive performance.

Furthermore, liquid biopsy and single-cell/spatial omics enhance real-time monitoring of disease progression and treatment response, addressing challenges posed by intratumoral heterogeneity. This review synthesizes recent advances in GBM biomarker research across multiple omics layers, emphasizing their complementary roles in unravelling tumor biology, guiding personalized treatment, and shaping future therapeutic strategies.

We highlight the importance of incorporating molecular methods to improve diagnostic accuracy and achieve personalized treatments for gliomas, as proposed by the current 2021 WHO CNS 5 tumor classification guidelines. Performing new studies with larger patient cohorts integrating clinical data is necessary to determine the behavior, epidemiology, and therapeutic outcomes of this type of tumor more comprehensively.

The present analysis of prognostic outcome associations of PA-PPI use in patients with recurrent glioblastoma provides no evidence that PA-PPI use may compromise outcome in this setting. The disconnect between clear outcome associations in the first-line setting, without a link to MGMT promoter methylation, versus no associations in the recurrent setting may be linked to changing prescriptions patterns, but requires further studies. Since alternative medications are available, the indications for PA-PPI prescription should probably be narrowed in patients with glioblastoma.

Our findings suggest gross total resection of contrast-enhancing tumour and MGMT promoter methylation are strongly associated with improved survival following first recurrence of glioblastoma. Conversely, age, preoperative KPS, adjuvant chemotherapy, and timing of re-resection showed inconsistent or non-significant associations, emphasizing the need for prospective studies to refine prognostic assessments and guide individualized treatment strategies in recurrent glioblastoma.

P1/2, N=27, Recruiting, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano | Phase classification: P1b --> P1/2 | N=18 --> 27 | Trial completion date: Jan 2023 --> Jan 2027 | Trial primary completion date: Dec 2022 --> Apr 2026

Finally, we identify a 17-gene CMP signature, termed Matrisome 17 (M17), which is a stronger prognostic factor compared to MGMT promoter methylation status as well as canonical subtypes, and importantly, may predict responses to PD1 blockade. Patient stratification based on matrisome profiles can contribute to the selection and optimization of treatment strategies.