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Fig. 2 | Breast Cancer Research

Fig. 2

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

Fig. 2

Targeting PI3K/mTOR signaling overcomes resistance to CDK4/6 inhibitors. a Effect of palbociclib and alpelisib alone and in combination in EFM19 and EFM-PR cells. Graphed as % inhibition of cell generation. b Effect of palbociclib (200 nmol/L) and aleplisib (200 nmol/L) monotherapy and combination on Rb, ER, and AKT signaling. Lysates collected 24 h post-dose. c Growth curves for EFM19-PR xenografts progressing on palbociclib (P)/fulvestrant (F) prior to randomization and treatment with the indicated therapeutics; 8 mice per arm (mean tumor volume ± SEM). d Snap-frozen xenograft tissue, collected at the end of the study from the EFM19-PR xenografts analyzed by Western blot for the indicated proteins. “Parental control” indicates xenograft tissue collected from vehicle control-treated EFM19 xenografts (Fig. 1d). CK-19 is a marker of human epithelial cell content in the snap-frozen xenograft sample; however, CK-19 expression is low in the EFM19 cells, as such α-tubulin was used as a loading control. e HCC1500 xenografts treated with ribociclib and fulvestrant QD until progression before re-randomization into the indicated treatment groups; 8 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, and fulvestrant 5 mg/mouse QW by subcutaneous injection. *Statistically significant difference compared to control (palbociclib + fulvestrant); P < 0.05

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