mTOR inhibitors sensitize BRCA-proficient TNBC xenografts to PARP inhibitors.
A-C. Female nude mice (10 per group) with orthotopically implanted MDA-MB-231 xenografts were treated by oral gavage with vehicle control, everolimus (EVE, 3 mg/kg), BMN 673 (BMN, 0.333 mg/kg) or a combination of both agents daily for 6 weeks. A. Tumor volumes were determined on the indicated days of treatment. Results are shown as means±SEM. Two-way analysis of variance was used to determine statistical significance of differences between groups: *P < 0.001 (BMN+EVE vs EVE); #P = 0.0143 (BMN+EVE vs BMN). B. Representative pictures of orthotopically implanted tumor tissue from each group at the time of study termination (day 42). C. Body weight-time curve in MDA-MB-231 xenograft is shown. D–F. Female nude mice (8 per group) with orthotopically implanted BT-549 xenografts were treated by oral gavage with vehicle control, EVE (3 mg/kg), BMN (0.333 mg/kg), or a combination of both agents daily for 8 weeks. D. Tumor volumes were determined on the indicated days of treatment. Results are shown as means±SEM. Two-way analysis of variance was used to determine statistical significance of differences between groups: *P < 0.001 (BMN+EVE vs EVE; BMN+EVE vs BMN). E. Pictures of orthotopically implanted tumor tissue from each group at the time of study termination (day 56). F. Body weight-time curve in BT-549 xenograft is shown.