Finally, ZSTK474 prolonged overall survival in Cre-LoxP conditional transgenic <i>Pten;p16<sup>Ink4a</sup>/p19<sup>Arf</sup>;K-Ras<sup>v12</sup>;LucR</i> mice, mainly by delaying tumor onset.<b>Conclusions:</b> PI3K/mTOR inhibitors with weak affinities for ABC transporters can achieve target inhibition in brain (tumors), but have modest single-agent efficacy and combinations with (BBB penetrable) inhibitors of other activated pathways may be required.<i></i>.
Failure of brain cancer treatment may be in part due to limitations in drug delivery, influenced by the ABC drug efflux transporters P-gp and BCRP at the blood-brain and blood-tumor barriers, in brain tumor cells, as well as in brain tumor stem-like cells.