However, monotherapy using PI3K inhibitors or upstream RTK targeting has thus far proven to be insufficient in clinical trials for DIPG and other cancers.12,13 Besides poor BBB penetration, resistance may be due to activation of alternative signaling pathways that compensate for PI3K/AKT/mTOR inhibition and allow tumor cells to evade the antiproliferative effects of monotherapy.14 Combination therapy targeting multiple pathways may thus be a more effective strategy. Here, AKT1 is linked to neoplasm.