Fig. 7.

DS-6051b induced a marked tumor shrinkage to SLC34A2-ROS1-G2032R mutation harboring HCC78xe3 cells. a–d Mice-bearing SLC34A2-ROS1 (WT or G2032R) induced HCC78xe3 cells were treated with crizotinib and DS-6051b. HCC78xe3-SLC34A2-ROS1-WT (a) or -G2032R (c) cells were implanted into mice. DS-6051b (50 and 100 mg/kg) and crizotinib (50 and 100 mg/kg) were given once daily by oral gavage for the indicated period; N = 6. In these experiments, DS-6051b was dissolved in 0.5% MC, and crizotinib was in 0.01 N HCl. Kaplan–Meier curves of the survival of the mice in each treatment arm are shown in (b) and (d). The results in (a, c) are indicated as mean ± s.d.; **P < 0.01 (Mann–Whitney U test). e Mice-bearing SLC34A2-ROS1 (WT or G2032R) induced HCC78xe3 cells were orally administered DS-6051b at 50 and 100 mg/kg, or crizotinib at 50 and 100 mg/kg once a day for 3 days. After 3 days of each drug treatment, the tumors from two mice of each treatment groups were collected and were lysed. The indicated proteins were detected by immunoblot analysis using corresponding antibodies