for the treatment of glioma

One barrier to successful treatment of malignant glioma is resistance to alkylating agents such as temozolomide. The cytotoxic activity of temozolomide and other alky-lating agents is believed to manifest largely by the forma-tion of O6-methylguanine DNA adducts. Consequently, the primary mechanism of resistance to temozolomide is a function of the activity of the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT). Fortuitously, MGMT is inactivated after each reaction (i.e., suicide enzyme). Therefore, if the rate of DNA alky-lation were to outpace the rate of MGMT protein syn-thesis, the enzyme could, in theory, be depleted. Several studies have shown that prolonged exposure to temo-zolomide can deplete MGMT activity in blood cells, a process that could potentially increase the antitumo