In Vivo Validation of Targeted Therapies

The following reagents were used for in vivo validations upon randomization of tumor bearing NSG mice: MK-8669/Ridaforolimus as an allosteric mTORC1 inhibitor (1mg/kg, 5IW), BKM120/Buparlisib as a pan-PI3K and BYL719 and GDC0032/Taselisib as PI3K-alpha inhibitors (27.5, 35mg/kg 6IW and 5 mg/kg, respectively), LEE011/Ribociclib as a CDK4/6 inhibitor (75mg/kg), AZD2281 (Olaparib/Lynparza) as a PARP inhibitor (50mg/kg, 5IW), AZD1775 as Wee1 inhibitor (120mg/kg, 5dON 9dOFF) and Tamoxifen (10mg/ml, 100μl daily) as an ER pathway inhibitor. Tumor volumes were normalized to the starting tumor volume and mean volumes were plotted and compared to vehicle-treated controls. Details such as number of mice used and mean volumes per treatment arm are shown in Table S7.
All experimental procedures were approved by the University of Cambridge Animal Welfare and Ethical Review Committee and by the Vall d’Hebron Hospital Clinical Investigation Ethical Committee and Animal Use Committee.