In summary, these data at least partially indicate that acalabrutinib–rapamycin combination therapy impairs tumorigenesis through the suppression of GBM stemness signaling and negative modulation of the BTK/Akt/mTOR signaling pathway, ultimately affecting angiogenesis and vascular normalization in vitro and in vivo and that this combination therapy can be used as a therapeutic strategy with promising efficacy for patients with GBM. This evidence concerns the gene MTOR and glioblastoma.