Addition of the dual PI3K/mTOR inhibitor PI-103 to erlotinib was necessary to induce growth arrest of human glioma cell lines with mutant PTEN [69], suggesting that activation of the PI3K/Akt/mTOR pathway by EGFR-independent mechanisms confers resistance to EGFR inhibitors, but that this resistance can be overcome by the addition of pathway inhibitors. This evidence concerns the gene PTEN and central nervous system cancer.