MTOR and Cowden syndrome 1: These findings are consistent with previous reports that BEZ or a related PI3K/mTOR inhibitor can have significant anti-cancer/therapeutic effects in malignancies, including high-grade CS [98,99,100], and that BEZ235 can enhance the cytotoxic effects of DOX in malignancies [86,88], in part due to the BEZ-mediated increased accumulation of DOX [87].