mTOR, a key effector of PI3K/AKT signaling, is implicated in cell survival, metabolic reprogramming, and GBM cell proliferation.267 Both mTORC1 and mTORC2 contribute to GBM progression, with mTORC1 promoting glycolysis via HIF-1 activation and mTORC2 enhancing tumor cell motility through RICTOR overexpression.10,268 Additionally, alternative activation pathways, such as PKCα-mediated EGFR-mTOR signaling, indicate that multiple regulatory inputs sustain mTOR activity in GBM.269 The complexity of PI3K/AKT/mTOR signaling in GBM necessitates a multifaceted therapeutic approach. This evidence concerns the gene HIF1A and glioblastoma.