MGMT Status as a Clinical Biomarker in Glioblastoma

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.