In light of results obtained in this work, we propose the dual inhibition of MGMT, responsible for removing O6-methylguanine, and MPG, which initiates the BER pathway by excising N7, N3 methyl purines, as a strategy to overcome TMZ resistance in those group of glioblastomas with the following signature: ATRX-wt/p53-mut, ATRX-mut/p53-wt and ATRX-mut/p53-mut (Fig. 4), which represent, as mention before, approximately 60% of all glioblastomas. Here, MGMT is linked to glioblastoma.