PTEN, a critical tumor suppressor, negatively regulates the PI3K/AKT/mTOR pathway, and its loss further exacerbates GBM aggressiveness.264 The inhibition of mTOR with rapamycin has demonstrated promising effects in vitro, but clinical trials have shown limited efficacy,265 suggesting the need for combination therapies. This evidence concerns the gene PIK3CA and glioblastoma.