Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Glioblastomas with methylation of the promoter region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promoter methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative methylation threshold for better survival among patients with glioblastomas. Methods: We included consecutive patients ≥18 years treated at our department between 11/2010 and 08/2018 for a glioblastoma, IDH wildtype, undergoing quantitative MGMT promoter methylation analysis. The primary endpoint was overall survival. Results: A total of 321 patients were included. Median overall survival was 12.6 months. Kaplan−Meier and adjusted Cox regression analysis showed better survival for the groups with 16−30%, 31−60%, and 61−100% methylation. In contrast, survival in the group with 1−15% methylation was similar to those with unmethylated promoter regions. A secondary analysis confirmed this threshold. Conclusions: Better survival is observed in patients with glioblastomas with ≥16% methylation of the MGMT promoter region than with <16% methylation. Survival with tumors with 1−15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264886 | PMC |
| http://dx.doi.org/10.3390/cancers14133149 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Temozolomide-Derived Therapeutic Strategies to Overcome Resistance in Glioblastoma.
J Med Chem
September 2025
Department of Chemistry and Biochemistry, The University of Texas at El Paso, El Paso, Texas 79968, United States.
Glioblastoma multiforme (GBM) accounts for nearly half of malignant CNS tumors and has a dismal 5-year survival rate of 5.5%. The current standard of care comprises maximal surgical resection, followed by radiotherapy with concurrent temozolomide (TMZ) and subsequent adjuvant TMZ chemotherapy.
View Article and Find Full Text PDFPurpose Recent studies show that glioblastoma (GBM) is more sensitive to Temozolomide (TMZ) in the morning. In cells, inhibiting O6-Methylguanine-DNA-Methyltransferase (MGMT) abolished time-dependent TMZ efficacy, suggesting that circadian regulation of this DNA repair enzyme underlies daily TMZ sensitivity. Here, we tested the hypotheses that MGMT-promoter methylation and protein abundance vary with time-of-day in GBM, resulting in daily rhythms in TMZ efficacy.
View Article and Find Full Text PDFGenetic and epigenetic landscape of O-methylguanine-DNA methyltransferase (MGMT): implications for DNA repair and cancer therapeutics.
Explor Target Antitumor Ther
August 2025
Women's Biomedical Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
O-Methylguanine-DNA methyltransferase (MGMT) acts as a genomic custodian, reversing alkylation damage to preserve DNA integrity. However, when its regulatory balance tips via promoter methylation, polymorphisms, or epigenetic silencing, MGMT can become a liability, fuelling cancer progression, treatment resistance, and poor outcomes across malignancies. This review uncovers the nuanced control of MGMT, revealing how its genetic and epigenetic shifts shape tumor behavior, therapeutic response, and risk stratification.
View Article and Find Full Text PDFAdvanced MRI, Radiomics and Radiogenomics in Unravelling Incidental Glioma Grading and Genetic Status: Where Are We?
Medicina (Kaunas)
August 2025
Neuroradiology Unit, NESMOS (Neuroscience, Mental Health and Sensory Organs) Department, Sant'Andrea Hospital, La Sapienza University, Via di Grottarossa, 1035-1039, 00189 Rome, Italy.
The 2021 WHO classification of brain tumours revolutionised the oncological field by emphasising the role of molecular, genetic and pathogenetic advances in classifying brain tumours. In this context, incidental gliomas have been increasingly identified due to the widespread performance of standard and advanced MRI sequences and represent a diagnostic and therapeutic challenge. The impactful decision to perform a surgical procedure deeply relies on the non-invasive identification of features or parameters that may correlate with brain tumour genetic profile and grading.
View Article and Find Full Text PDFFirst-in-human study of an EGFRvIII x CD3 T cell bispecific antibody in the treatment of newly diagnosed glioblastoma.
Neurooncol Adv
July 2025
Department of Medicine, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Background: This first-in-human study evaluated EGFRvIII × CD3 TCB, a novel T cell bispecific antibody, in patients with newly diagnosed EGFRvIII-positive glioblastoma.
Methods: Patients with newly diagnosed glioblastoma received escalating doses of EGFRvIII × CD3 TCB following chemoradiation. The primary objectives were to evaluate safety/tolerability and define the maximum tolerated dose (MTD); secondary objectives included pharmacokinetics (PK), immunogenicity, pharmacodynamics, and clinical activity.