These disappointing results can, at least in part, be explained by (i) the inability to deliver more effective anticancer agents, as Dox, into the CNS across the BBB, avoiding various resistance mechanisms, including the active efflux of anticancer drugs mediated by ATP-binding cassette (ABC) transporters as P-gp [13]; (ii) the acquisition of adaptive and resistance mechanisms of GBM cells in the presence of prolonged treatment with metabolic activity modulators, such as Rapa [14]. Here, PGP is linked to glioblastoma.