The increased activity of the insulin pathway promoted by paxalisib treatment in DIPG xenograft mouse models was rescued using metformin (Figure 3, C and D), a strategy that effectively dephosphorylated the INSR, promoted increased phosphorylation of tumor suppressor TSC2 at Thr1462, and reduced tumor burden as measured by H3K27M+ and Ki67+ cells (Figure 3, C and D). Here, TSC2 is linked to neoplasm.