Fig. 5

Combined targeting of ER, CDK4/6, and PI3K/mTOR in treatment-naive ER+/HER2− breast cancer xenografts. a, b ZR751 and MCF7 xenografts treated with ribociclib alone or ribociclib in combination with fulvestrant or alpelisib/fulvestrant or everolimus/fulvestrant (8 mice per arm, mean tumor volume ± SEM). c HBX34, a PIK3CA/PTEN wild-type PDX breast cancer model, treated with letrozole in combination with alpelisib/ribociclib. Treatment was withdrawn after 55 days, and measurements were continued for a further 40 days post-withdrawal of drug treatment. Dashed lines represent previously published data. d Growth curves of the individual mice (colored lines) from the MCF7 xenograft study depicted in b where treatment was withdrawn after 28 days and tumors were monitored for up to 9 weeks for progression. For all experiments, the following dose schedule was used: ribociclib 75 mg/kg PO QD, alpelisib 35 mg/kg PO QD, everolimus 10 mg/kg PO QD, letrozole 2.5 mg/kg PO QD, and fulvestrant 5 mg/mouse QW by subcutaneous injection. *Statistically significant difference compared to vehicle control; P < 0.05