Fig. 3.

ABT-700 shows antitumor activity in preclinical models of tumor xenografts of human cancer cells harboring MET amplification. a Tumor growth curves of SNU5 gastric cancer treated with ABT-700. SCID mice with established tumors were treated with ABT-700 in a dose response administered by intra-peritoneal injections every 21 days. Each group had 6 mice; all ABT-700 treatment groups show significant difference (P value <0.0001 indicated by ****) when compared to the control group (day 4–28); high dose (10–40 mg/kg) groups are significant different from 5 mg/kg group (P value <0.0001 indicated by ++++) for day 4–63. b IHC analysis of SNU5 tumors treated with ABT-700. As in (a), tumors from mice treated with a single dose of ABT-700 at 10 mg/kg or vehicle control for 7 or 21 days were harvested and subjected to IHC analysis for markers as indicated. Representative images of one tumor are shown. c Tumor growth curves of EBC1 tumor xenograft model. SCID mice with established tumors were treated with ABT-700 in dose response administered by intra-peritoneal injections every 21 days. Each group had 5 mice; all ABT-700 treatment groups show significant difference (P value <0.0001 indicated by ****) when compared to the control group (day 4–31); high dose (20–40 mg/kg) groups are significant different from 10 mg/kg group (P value <0.0001 indicated by ++++) for day 4–42. d Tumor growth curves of SNU620 gastric cancer treated with ABT-700. SCID mice with established tumors were treated with ABT-700 in dose response administered by intra-peritoneal injections every 21 days. Each group had 6 mice; all ABT-700 treatment groups show significant difference (P value <0.0001 indicated by ****) when compared to the control group (day 4–28); there was no significant difference among treatment groups (day 4–28). e Survival curves of mice with metastatic EBC1 tumors treated with ABT-700. Primary tumors established after subcutaneous inoculation of EBC1 cells were surgically removed and ABT-700 at 10 mg/kg, Q21D, was administered with several schedules (start and end day) as shown. Growth of metastases in the lung caused death of animals and mortality was monitored over 530 days. Each group had 7 mice; comparison of survival curves by Log-rank (Mantel-Cox) test showed significance with P value <0.01 indicated by ** or <0.05 indicated by * as compared to the control group