Figure 1. PML mediates resistance to mTOR targeted therapies in GBM, which is reversed by ATO. (A) Schematic diagram showing that persistent mTOR signaling promotes tumor cell proliferation, while PML opposes it. (B) In GBMs treated with mTOR inhibitors or EGFR inhibitors such as erlotinib that also block mTOR signaling, PML is upregulated, promoting tumor cell arrest. (C) ATO, which leads to degradation of PML protein, synergizes with mTOR inhibitors, potently causing tumor cell death.