MTOR and breast cancer: Based on this evidence, PI3K inhibitor such as LY294002 (Clark et al., 2002), S6K1 inhibitor H89 (Becker et al., 2011), MAPK inhibitor U0126 (Becker et al., 2011; Casa et al., 2012), and dual PI3K/mTOR inhibitor NVP-BEZ235 (Brachmann et al., 2009) have been studied in pre-clinical and clinical studies supported by the hypothesis that combinations of AKT and IGF-IR/InsR inhibitors would be an effective treatment against hormone-independent ER + BC (Fox et al., 2013).