MGMT and glioblastoma: Other avenues for overcoming MGMT-mediated TMZ resistance in GBM involve dual inhibition of base excision repair and NAD+ biosynthesis; blocking base excision repair results in hyperactivation of poly(ADP-ribose) polymerase as the cell attempts to repair TMZ-mediated damage without the appropriate excision repair pathways, and the cell ultimately dies from energy depletion induced by the accumulation of repair intermediates [37].