Overall, our results demonstrate that in MB cells the PI3K inhibitor MEN1611 rescues the Ptch1+/−/Tis21KO-dependent activation of the PI3K/AKT/mTOR pathway, in parallel with a decrease of tumor growth and increased death of MB stem cells, and point to treatment with MEN1611 as a promising approach for cancer therapy of MBs harboring the Tis21 ablation. The gene discussed is BTG2; the disease is Mobius syndrome.