TITLE:
Refining Prognostic and Predictive Models in Glioblastoma: A Comprehensive Literature Review of MGMT Promoter Methylation and IDH1 Mutations
AUTHORS:
Sarayu Ganganalli, Prahlad Parajuli
KEYWORDS:
Glioma, Glioblastoma Multiforme (GBM), Isocitrate Dehydrogenase 1 (IDH1), O6-Methylguanine-DNA Methyltransferase (MGMT)
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.13 No.8,
August
20,
2025
ABSTRACT: Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor in adults with limited treatment options and a median survival of 12 - 15 months. In recent years, molecular biomarkers have emerged to assist with individualized treatment and improve prognostic calculations. This narrative literature review presents a summary with findings from peer reviewed research targeting two of the most clinically significant biomarkers currently in GBM, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase 1 (IDH1) mutations. MGMT methylation has shown strong predictive value for predicting which patients will respond to alkylating chemotherapy, specifically temozolomide, which is the standard of care (SOC) in GBM. IDH1 mutations are useful and reliable prognostic biomarkers for predicting better survival and slower tumor growth in GBM patients. Importantly, research shows that, in patients with both MGMT and IDH1 mutations together, their clinical outcomes are more favorable than patients with only one or the other. While the evidence is promising, the variations between methodology and the need for standardized processes in evidence, combined with current practice, has also been a drawback for clinical utility. This review includes some emerging therapies, diagnostic technologies, as well as a perspective on future research aiming to improve the usage of MGMT and IDH1 in personalized treatment approaches of glioblastoma. These examples built upon the understanding of biomarkers in GBM represent a necessary instrument towards further positioning glioblastoma management from a general approach to individualized approach.