Fig. 3: Combined inhibition of CDK4/6 and AKT prevents progression in tumor xenografts resistant to fulvestrant.

Tumor growth curves of MCF-7 (A) and 182R-1 (B) tumors following treatment with fulvestrant (Fulv, 100 mg/Kg bodyweight; N = 7) or vehicle (castor oil, N = 8) administered subcutaneously once a week. Treatment was initiated when tumors reached 50 mm3 and continued for 5 weeks. C Mice were sacrificed on week 5 and MCF-7 and 182R-1 tumors were excised. Tumor growth curves of 182R-1 tumors treated with CDK4/6 inhibitor (CDK4/6i, palbociclib, 50 mg/Kg bodyweight; N = 8) alone (D), in combination with fulvestrant (100 mg/Kg bodyweight; N = 7 and N = 10) (D and E), or in combination with both AKT inhibitor (AKTi, capivasertib 100 mg/Kg bodyweight) and fulvestrant (100 mg/Kg bodyweight; N = 6 and N = 10) (D and E), or vehicle (castor oil and 25% w/v HPB cyclodextrin; N = 8) (D). CDK4/6i and AKTi were administered by oral gavage once daily for 5 days a week when tumors reached 50 mm3 (D) or 250 mm3 (E), and treatment was continued for up to 8 weeks. Data are shown as mean tumor volume ± SEM. Asterisks indicate a significant difference in ANOVA one-way test (D) or two-tailed t-test (A, B and E) at the endpoint (*0.01 < p < 0.05, **0.001 < p < 0.01, ***0.0001 < p < 0.001 and ****p < 0.0001).