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Fig. 6 | Breast Cancer Research

Fig. 6

From: Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer

Fig. 6

Combined EZH2/ATM inhibition shows an enhanced anti-tumor effect in KB1P mammary tumor allografts. A Mammary tumor tissue fragments from KB1P mice were transplanted into the fourth mammary fat pad of FVB females and treatments were initiated following tumor outgrowth to approximately 100 mm3 (100%). Upon tumor detection (day 0), mice were treated for 28 consecutive days. B Relative tumor volume curves. Tumor size was measured twice a week. For a better comparability, the tumor volume at day x was normalized to the initial tumor volume at treatment start (day 0) and defined as relative tumor volume (RTV). C Progression-free survival curves of KB1P mammary tumor-bearing mice treated with vehicle (grey), GSK126 (150 mg/kg i.p.) single agent (dotted line), AZD1390 (2 × 20 mg/kg, oral gavage) single agent (dashed line), or combined treatment with GSK126/AZD1390 (black). Progression-free survival was defined as the time to develop a 10-time increase in tumor volume. Survival curves were generated with the Kaplan–Meier approach and compared with the log-rank test as indicated. Censored animals (n = 3) are indicated by tick marks. D Representative images of immunofluorescence staining of EZH2, H3K27me3 and phosphorylated ATM in mammary tumor tissue after treatment as indicated. Scale bar 200 µm

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