PIK3CA and glioblastoma: In addition, PI3K inhibitors have also been shown to enhance TMZ cytotoxicity in GBM via distinct mechanisms, such as downregulation of ATP-binding cassette subfamily E member 1, inhibition of autophagy, promotion of apoptosis, and inhibition of DNA double-strand break repair (Gil del Alcazar et al., 2014; Radoul et al., 2016; Zhang et al., 2018; Zajac et al., 2021).