Figure 4. The combination of AZD8055/ABT-263 has in vivo efficacy in KRAS mutant CRC.

(A) Cohorts of KRAS MT SW620 xenograft tumors (left panel) were treated with no drug (control), AZD8055 (16 mg/kg/qd), ABT-263 (80 mg/kg/qd), or the combination (16 mg/kg/qd AZD8055, 80 mg/kg/qd ABT-263). Average tumor sizes for each treatment group are plotted. Cohorts of KRAS wild-type KM12 xenograft tumors (right panel) were treated with vehicle control or AZD8055/ABT-263 combination, and average tumor sizes are plotted. (B) Approximately three hours following the final drug treatment, mice were euthanized and tumors were harvested. Protein lysates were prepared from SW620 (left) and KM12 (right) tumors and were subjected to Western blot analyses with the indicated antibodies. (C) Representative images of tumors taken from serial colonoscopies of KRAS MT and KRAS WT GEMMs as treated in (A). Arrows depict each tumor. Tumor size was calculated by determining the percent occlusion of the lumen as described in Materials and Methods. (D) Colorectal cancers in KRAS MT and KRAS WT GEMMs were treated as in (A) for 28 days and changes in tumor volume for each mouse are shown by a waterfall plot. (E) Lysates from KRAS WT GEMM tumors were harvested approximately three hours following the last drug treatment of the experiment, and protein lysates were subjected to Western blotting analyses with the indicated antibodies. Each number represents a different tumor.