AKT1 and central nervous system neoplasm: Although prior studies have demonstrated RTK and downstream PI3K/AKT/mTOR amplifications in DIPG, monotherapy against the PI3K pathway has failed to show a significant tumor response in various malignancies including DIPG and other CNS tumors.7,8,12,13 We have previously shown how combinatorial therapy resulted in increased caspase-dependent apoptosis.10 In this study, two CED injections were used to best approximate our clinical experience, where one or two CED injections are used in patients.5