O6-methylguanine DNA-methyltransferase (MGMT) is a DNArepair protein that removes alkyl groups from the O6 position of guanine and therefore blunts the cytotoxic effect of alkylating drugs, including temozolomide (TMZ). Epigenetic silencing of the MGMT gene through promoter methylation is associated with diminished DNArepair activity; this event has been linked with a better response to alkylating drugs and with an improved outcome in malignant glioma. The 2-year analysis of the milestone multicenter randomized EORTC-NCIC trial confirmed the prognostic and predictive role of MGMT promoter methylation for response to TMZ in glioblastoma (GBM). The 5-year analysis of survival data from the same trial confirmed the prognostic role of MGMT promoter methylation but resized its predictive value for response to TMZ. Recently, the prognostic role of MGMT promoter methylation in GBM has been confirmed in a large phase III trial comparing standard-dose and doseintensified TMZ in newly diagnosed GBM.
Last date updated on June, 2014