A drug screening aimed at evaluating the potential recycling and repurposing of known drugs was conducted in TMZ-resistant GBM cell lines and primary cultures of newly diagnosed GBM with different MGMT promoter methylation status, phenotypic/genotypic background and subtype, and validated with sphere formation, cell migration assays, and quantitative invasive orthotopic in vivo models.
A novel molecular recursive partitioning analysis classification has recently been reported integrating the MGMT promoter methylation (MGMTmeth) and IDH1 mutation (IDH1mut) status for glioblastoma (GBM-molRPA) patients treated with temozolomide-based chemoradiation.
After irradiation and exposure to steroid and temozolomide 6 and 24 h later, a methylated MGMT promoter and negative protein expression were seen in U343 glioblastoma cell lines which have methylated promoter and negative protein expression.
After the administration of temozolomide concomitant with and adjuvant to radiotherapy in patients with glioblastoma, the pattern determined by [(18)F]FET-PET seems to be associated with MGMT methylation status.
After the administration of TMZ concomitant with and adjuvant to RT in patients with GBM, the pattern of, and time to, recurrence are strictly correlated with MGMT methylation status.
Age at initial diagnosis, Karnofsky performance score, and O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status are the most well-documented predictors of survival in patients with newly diagnosed glioblastoma.
Although methylation of the O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) gene promoter predicts response to temozolomide in patients with glioblastoma, no consensus exists as to which assay is best for its detection.
Although the two classical molecular markers of glioblastoma including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation are associated with overall survival rate of glioblastoma patients, they are not specific to the survival outliers.
Although this data is from a retrospective analysis using small number of patients, the study might indicate that concomitant use of temozolomide with radiotherapy is a crucial step in the standard treatment for glioblastoma patients with MGMT promoter methylation.
Although this resistance has frequently been linked to the expression of O6-methylguanine-DNA methyltransferase (MGMT) it seems that this enzyme is not the only molecular mechanism that may account for the appearance of drug resistance in glioblastoma multiforme patients as the mismatch repair (MMR) complex, P-glycoprotein, and/or the presence of cancer stem cells may also be implicated.
Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas.
Based on an univariate or multivariate analysis between different race (Caucasian and Asian), a meta-analysis of the effects of MGMT promoter methylation on both progression-free survival (PFS) and overall survival (OS) among GBM patients was conducted.
Because both autophagy and MGMT overexpression have been implicated to TMZ-induced drug resistance in glioblastoma, our results showed that pine needle extract and chrysin may serve as a potential anticancer agent against glioblastoma, especially with regard to sensitizing glioblastoma cells resistant to TMZ.