Figure 6. PARP inhibition synergizes with 17β-estradiol against tumors in vivo and prevents recurrence.

(A/B) Ovx mice bearing tumors ~200 mm³ were randomized to treatment as indicated. E2 was delivered continuously, and olaparib was administered daily for 28 d (gray shading). Data are shown as mean + SEM. (C) After 10 wk of treatment in (A), mice without palpable tumors were monitored for recurrence. Time to recurrence was calculated as time from treatment start until tumors re-grew to baseline volume. Proportions of mice that were recurrence-free over time are shown. (D) Ovx mice bearing WHIM16 tumors were treated as in (A), and tumors were harvested 4 h after drug treatment on Day 2. Tumor lysates were analyzed by immunoblot. vinc.- vinculin loading control. (E) Mice bearing tumors that recurred during E2 monotherapy in (C) were treated with estrogen deprivation starting on Day 0, which stunted tumor growth. Each line represents one mouse. Tumors eventually resumed growth, which was defined as two consecutive biweekly volume measurements above baseline. (F) Mice with tumors that resumed estrogen-independent growth in (D) were randomized to treatment with a second cycle of E2 ± olaparib. Data are shown as mean + SEM. ***p<0.0005, n.s. = not significant.