The role of STAT3 in GBM pathogenesis is still under debate, as it is unclear whether it is pro-oncogenic or tumor-suppressive [47,48], and recent reports suggest a feedback activation mechanism in STAT3, rather than inhibition, in response to the inhibition of the PI3K/Akt/mTOR signaling pathway [49]. This evidence concerns the gene STAT3 and glioblastoma.