Fig. 6

PD Biomarker analysis of responses to combined targeting of ER, CDK4/6, and PI3K/mTOR in treatment-naive ER+/HER2− breast cancer cell line xenografts. a MCF7 xenografts treated with ribociclib (75 mg/kg PO QD) monotherapy or combination with fulvestrant (5 mg/mouse QW), alpelisib (35 mg/kg PO QD), or everolimus (10 mg/kg PO QD) (4 mice per arm, mean tumor volume ± SEM). b Effect of ribociclib alone and in combination with fulvestrant on selected proteins associated with cell cycle regulation by RPPA analysis. c Effect of alpelisib alone and in combination with fulvestrant on selected proteins associated with PI3K/mTOR signaling. d Comparing the effects of the triple combination versus the double combinations on proteins selected form both cell cycle and PI3K/mTOR pathways. e Heatmap showing all proteins (n = 76) with significant fold change (< 0.25 down (n = 56) or < − 0.25 up (n = 20)) in expression in response to the triple combination treatment relative to xenografts from control-treated mice. Expression changes for the same set of proteins in response to mono or combination therapy are also shown. Error bars represent ± SEM