MGMT Status as a Clinical Biomarker in Glioblastoma

MGMT promoter methylation status is a widely accepted biomarker in glioblastoma. Inconsistencies between MGMT promoter methylation status and expression level have raised the question of the value of promoter methylation status in predicting patient response to temozolomide treatment in glioblastoma. Combined evaluation of MGMT methylation and expression and/or mismatch repair proficiency may provide better insight into a personalized treatment approach. Understanding the molecular and genetic mechanisms regulating MGMT expression beyond promoter methylation is essential to enhance the utility of MGMT status as a biomarker in treatment decision-making for glioblastoma patients. Glioblastoma is the most common primary malignant brain tumor. Although current standard therapy extends median survival to ~15 months, most patients do not have a sustained response to treatment. While O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) promoter methylation status is accepted as a prognostic and promising predictive biomarker in glioblastoma, its value in informing treatment decisions for glioblastoma patients remains debatable. Discrepancies between MGMT promoter methylation status and treatment response in some patients may stem from inconsistencies between MGMT methylation and expression levels in glioblastoma. Here, we discuss MGMT as a biomarker and elucidate the discordance between MGMT methylation, expression, and patient outcome, which currently challenges the implementation of this biomarker in clinical practice. Glioblastoma is the most common primary malignant brain tumor. Although current standard therapy extends median survival to ~15 months, most patients do not have a sustained response to treatment. While O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) promoter methylation status is accepted as a prognostic and promising predictive biomarker in glioblastoma, its value in informing treatment decisions for glioblastoma patients remains debatable. Discrepancies between MGMT promoter methylation status and treatment response in some patients may stem from inconsistencies between MGMT methylation and expression levels in glioblastoma. Here, we discuss MGMT as a biomarker and elucidate the discordance between MGMT methylation, expression, and patient outcome, which currently challenges the implementation of this biomarker in clinical practice. additional cancer treatment given after the primary treatment to decrease the risk of cancer recurrence. a class of anticancer drugs that interfere with cell DNA to kill tumor cells. a type of tumor originating from brain or spinal cord cells called astrocytes. a class of brain tumors that arise from cells called glia that surround and support nerve cells. an epigenetic mechanism where methyl groups are added to DNA molecules (in the context of DNA methylation), often modifying gene expression and function; promoter methylation refers to the addition of methyl groups to DNA sequences in the promoter region of a gene. a specialty that involves the management and study of central nervous system cancers, including tumors of the brain and spinal cord. (The Cancer Genome Atlas - Glioblastoma Multiforme) a dataset of glioblastoma as part of The Cancer Genome Atlas program that is built for cancer research. the transplantation of tissue or cells to an individual of another species. In this opinion article, it refers to a model of human tumor grown in immunodeficient mice.