EGFR and central nervous system cancer: 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.