Fig. 5.

Combined treatment of ovarian, prostate, and pancreatic tumor xenografts with TVB-3166 and paclitaxel inhibits tumor growth synergistically compared to single agent activity. A minimum of 10 mice per treatment group was used in all studies. (A) OVCAR8 ovarian adenocarcinoma cell line. (B) 22Rv1 castration-resistant prostate tumor cell line. (C) PANC1 pancreatic ductal adenocarcinoma tumor cell line. TVB-3166 was dosed once daily by oral gavage at 60 or 100 mg/kg. Paclitaxel was dosed once every 4 days by intravenous administration at 10 mg/kg. In groups dosed with both TVB-3166 (60 mg/kg) and paclitaxel (10 mg/kg), TVB-3166 was administered 2 h before taxane administration. Animals were randomized according to tumor size and drug treatment was started when the mean tumor size was 150–200 mm³. Tumors and blood samples were harvested 2 h after the last dose. TVB-3166 and paclitaxel plasma and tumor drug concentrations were determined by mass spectrometry. The in-life phase for these studies was performed at Crown Biosciences (Santa Clara, CA; Beijing, China).