Fig. 5: In vivo anti-tumour activity of the combination of capivasertib and fulvestrant in palbociclib insensitive models. | npj Breast Cancer

Fig. 5: In vivo anti-tumour activity of the combination of capivasertib and fulvestrant in palbociclib insensitive models.

From: Combining the AKT inhibitor capivasertib and SERD fulvestrant is effective in palbociclib-resistant ER+ breast cancer preclinical models

Fig. 5

A In vivo activity of capivasertib, fulvestrant and the combination in PI3K pathway mutated PDX tumour models (ST3632, ST3932, CTC174 and ST1799/HI/PBR) and PI3K pathway unaltered models ST3164B and ST941/HI/PBR. Tumours treated with vehicle (closed circles), 130 mg/kg capivasertib BID 4 days on 3 days off (open circles), 5 mg/animal fulvestrant, QW (open triangle), or combination (closed squares). Geomean tumour volumes ± SEM (*p < 0.05, **p < 0.005, ***p < 0.0005) are shown. B (i) Pharmacodynamic changes phosphorylation and total protein levels of PRAS40 (Thr246), S6 (Ser235/236) and p-4EBP1 (Thr37/46), pRb1 or ER in the CTC174 PDX PI3KCAm model after 28 days of treatment. Tumours treated with vehicle, 100 mg/kg capivasertib BID 4 days on 3 days off, 5 mg/animal fulvestrant, or combination. Data normalised to the geomean of β-actin and vinculin, percentage change from control plotted as mean ± SEM (n = 5). Statistical analysis ANOVA test vs vehicle-treated, *p < 0.05; **p < 0.005; ***p < 0.0005. (ii) Ki-67 was visualised using immunohistochemistry of tumour samples; represented as mean ± SEM (n = 5). Statistical analysis ANOVA test, *p < 0.05; **p < 0.01; ***p < 0.005, ****p < 0.001.

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