Owing to the extensive studies on TMZ-resistance in glioblastoma and other tumor types, researchers have identified non-MGMT related therapy resistance mechanisms such as the presence of intrinsically resistant glioma stem cell populations with an enhanced DNA repair ability (6, 23, 24), epigenetic alterations, dysregulated signaling cascades (25), thus adding additional complexity to TMZ resistance mechanism. This evidence concerns the gene MGMT and central nervous system cancer.