1. Fig. 4. Improved tumor response to docetaxel in TNBC and trastuzumab in HER2-amplified PDX models with the addition of S63845.
Improved tumor response to docetaxel in TNBC and trastuzumab in HER2-amplified PDX models with the addition of S Kaplan-Meier survival curves (left panels) and tumor volume curves (right panels) for PDX models. (A) TNBC PDX 110 from a BRCA1 mutation carrier (n = 10 to 12 mice per arm) and (B) TNBC PDX 838 (n = 10 to 11 mice per arm). Mice were treated with vehicle alone (black line), docetaxel (10 mg/kg intraperitoneally on days 1 and 22) plus vehicle for S63845 (blue line), S63845 (25 mg/kg intravenously once weekly for 6 weeks, on days 2, 9, 16, 23, 30, and 37) plus vehicle for docetaxel (green line), or combined docetaxel and S63845 (red line). (C) HER2-amplified PDX 231 (n = 6 to 8 per arm). Mice were treated with vehicle (black line), trastuzumab (30 mg/kg loading dose on day 1 and then 15 mg/kg twice weekly for 6 weeks starting on day 4) plus vehicle for S63845 (blue line), S63845 (25 mg/kg once weekly for 6 weeks on days 2, 9, 16, 23, 30, and 37) plus vehicle for trastuzumab (green line), or combined trastuzumab and S63845 (red line). For tumor volume curves, black bars indicate the total duration of the treatment. Mice, which remained otherwise healthy, were sacrificed when tumor size reached the experimental ethical end point (>600 mm3). Means ± SEM are shown. Log-rank (Mantel-Cox) P value is shown for combination therapy versus docetaxel or trastuzumab alone. Tumor growth curves for individual mice from PDX models 110, 838, and 231 are shown in fig. S10.
Delphine Merino et al., Sci Transl Med 2017;9:eaam7049
Published by AAAS