MGMT and glioblastoma: O6-methylguanine-DNA-methyltransferase (MGMT) is a primary factor in TMZ resistance.654,655 MGMT can repair damaged DNA by demethylation, thereby diminishing the anti-tumor effects of TMZ.656 The recurrent GBM is more insensitive to TMZ than the primary GBM due to higher MGMT expression.657 siMGMT can attenuate GBM resistance to TMZ by directly downregulating MGMT expression.