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Fig. 3 | Breast Cancer Research

Fig. 3

From: Targeting activated PI3K/mTOR signaling overcomes acquired resistance to CDK4/6-based therapies in preclinical models of hormone receptor-positive breast cancer

Fig. 3

Targeting PI3K/mTOR signaling blocks the progression on CDK4/6-endocrine-based therapy in PIK3CA mutant and wild-type ER+/HER2− breast cancers independent of continued CDK4/6 inhibition. a MCF7-PR xenografts treated with ribocicllib, alpelisib, or everolimus monotherapy. b HCC1500-PR xenografts treated with ribocicllib, alpelisib, or everolimus monotherapy. c MCF7-PR xenografts progressing on palbociclib/fulvestrant were randomized into 6 treatment groups for treatment with either alpelisib alone, no treatment, or palbociclib/fulvestrant combination for 21 days prior to switching to the indicated treatments for the 2nd treatment phase; 5 mice per arm. d The effect of the triple combination treatment on Rb, ER, and AKT signaling measured by Western blot analysis of snap-frozen tumor tissue collected at the end of the study. CK-19 was measured as a control for human epithelial cell content. e HCC1500-PR xenografts progressing on palbociclib/fulvestrant before randomization treatment groups as described above for 14 days prior to switching to the indicated treatments for the 2nd treatment phase; 7 mice per arm, mean tumor volume ± SEM. For all experiments, the following dose schedule was used: palbociclib 100 mg/kg PO QD, ribociclib 75 mg/kg PO QD, alpelisib 35 mg/kg PO QD, everolimus 10 mg/kg PO QD, and fulvestrant 5 mg/mouse QW by subcutaneous injection. *Statistically significant difference compared to control (palbociclib + fulvestrant); P < 0.05

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