Fig. 4.

AZD9496 is comparable to fulvestrant in delaying tumour growth and reducing ER level in endocrine-resistant tumours in vivo. Effect of AZD9496 and fulvestrant on in vivo transplantable model of MCF7 TamR (a–d, orange boxes) and MCF7 EDR (e, f, blue boxes). a Kaplan–Meier curves showing the tumour tripling time of MCF7 TamR tumours. Tumour volume is assessed in the presence of tamoxifen control (Tam), stop tamoxifen treatment and switch to drug vehicle (Veh), fulvestrant (Ful), or 3 different doses of AZD9496 (9496), 0.5, 5, and 50 mg/kg (for each group n = 12). Data are reported as change of the average of tumours in the same group. b ER protein levels by western blot and IHC (highlighted square in the western blot for the same sample) of representative short-term (10 days) treated tumours with quantification of ER protein level by IHC using H-score. c ER protein levels in representative long-term treated TamR tumours and quantification of ER protein level of the long-term treated tumours by IHC using H-score. d Heat map of significant differentially expressed genes in at least one of the treated groups compared to the tamoxifen control group. e Kaplan–Meier curves of transplantable MCF7 EDR tumours in the presence of vehicle (Veh; n = 7), fulvestrant (Ful; n = 6), or AZD9496 (9496; n = 6) for tumour tripling time from baseline followed up for about 90 days (±1–2 weeks). f Quantification of ER protein level by IHC using H-score. SEMs are shown; **p < 0.01; ****p = < 0.0001, ^#p < 0.01 compared to Tam and Veh, respectively. Cuzick test on (b and c) for Veh, 0.5, 5, and 50 mg/kg AZD9496 (not shown) p < 0.0001