Initial results revealed that TMZ: (i) induces reductions in GBM spheroid diameter (10–200 μM); (ii) demonstrates significant cytotoxicity (25–200 μM); (iii) exerts antiproliferative effects (≤25 μM) and promotes cell cycle arrest (G2/M phase) in Polκ KO spheroids when compared with WTE counterparts. Here, POLK is linked to glioblastoma.