As a result of its functional diversity, DNA-PKcs has been documented to play a critical role in the development of chemoresistance. Ganesh R. Panta et al noted that DNA-PKcs activated prosurvival NF-κB pathway through MEK/ERK signaling and opposed the apoptotic response following chemotherapeutic agent . Furthermore, Suk-Bin Seo et al reported that TRAIL inhibited the activation of DNA-PKcs/AKT/GSK-3β pathway and thereby sensitized tumor cells to vinblastine and doxorubicin . Thus, exploring the biologic function of DNA-PKcs and its mediated signaling may provide an ideal therapeutic target for overcoming TMZ resistance in glioma treatment.