Fig. 4

AZD7648 and liposomal doxorubicin synergize to inhibit tumour growth in vivo. a BT474. AZD7648 induces tumour regression in combination with liposomal doxorubicin in BT474 breast cancer xenografts (nude mice, vehicle and AZD7648 n = 12, liposomal doxorubicin n = 9, combination n = 11, geometric mean ± SEM). b AZD7648 induces tumour stasis in combination with liposomal doxorubicin in HBCx-17 TNBC PDX (nude mice, n = 10, geometric mean ± SEM). For a and b, corresponding mouse bodyweights and statistical analysis can be found in Supplementary Figs. 2C and 5A and Supplementary Table 3B. To assess tumour growth inhibition, a one-tailed, two-sample, t-test with unequal variances was used and for tumour regression, one-sample t-test analysis. c Pharmacokinetics of AZD7648 and pharmacodynamic modulation of DNA-PK biomarkers pDNA-PKcs Ser2056, pRPA32 Ser4/Ser8, and γH2AX after dosing of AZD7648 and liposomal doxorubicin in BT474 xenografts. Mice were dosed once with liposomal doxorubicin and with AZD7648 for 3 days. Samples were then collected 8 h after a last morning dose of AZD7648 on the fourth day. Measured by western blotting (nude mice, vehicle and liposomal doxorubicin n = 8, AZD7648 and combination n = 5, mean ± SEM). Significance assessed with two-sided t-tests performed on log-transformed data assuming unequal variance