Evaluating Efficacy of Targeted Therapies

NVP-BEZ235 (BEZ235), NVP-BKM120 (Buparlisib, BKM120), GSK1120212 (Trametinib, JTP-74057), PD0325901, and AZD6244 were purchased from Chemie Tek (Indianapolis, IN). Temozolomide, doxorubicin and paclitaxel were purchased from Sigma. For in vivo studies, BEZ235 and BKM120 were resuspended in NMP (N-methyl-2-pyrrolidone):PEG300 1:9 v:v, and GSK1120212 and PD0325901 were resuspended in 0.5% hydroxypropyl-methylcellulose (Sigma):0.2% Tween 80 (Sigma) (Gilmartin et al., 2011 (link); Kinross et al., 2011 (link)). BKM120, GSK1120212 and PD0325901 were given once daily by oral gavage at 10 ml/kg. Mice were treated with BEZ235 on a 5 days on, 2 days off schedule (Liu et al., 2009 (link)). Vehicle- and drug-treated mice were closely monitored on a daily basis for clinical signs as described above.