In vivo cetuximab sensitivity assay revealed diverse effect on 10 CTOS-derived xenogfrafts.
A, Growth curves of subcutaneous tumors originating from colorectal CTOS lines. Blue, treated with vehicle; orange, cetuximab (20 mg/kg); green, cetuximab (60 mg/kg). Mean±SD is shown. N = 4–6 in each treated group. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; 60 mg/kg cetuximab versus control; two-way ANOVA with Bonferroni post-test. Regression, partially responsive, and resistant are explained in the text. The type of KRAS mutant is indicated in superscript to the left of the line name. B, Microscopic images of vehicle-treated xenografts in A stained with EGFR antibody. Scale bar, 50 μm. Grading by staining intensity is shown. C, Waterfall plot of cetuximab-treated tumor growth (differences from baseline). The average sizes of cetuximab (60 mg/kg) treated tumors at day 21 were subtracted by the sizes at day 0 and the ratio compared to the average sizes at day 0 as follows: (VCmab (day 21)—VCmab (day 0))/ VCmab (day 0) x 100. Red bars, wildtype KRAS tumors; blue, KRAS mutants. D, Growth reduction from control (vehicle treated) tumors. The average sizes of vehicle-treated tumors at day 11 were subtracted by the sizes of tumors treated with cetuximab (60 mg/kg) and the ratio compared to the average sizes at day 11 as follows: (Vvehicle(day 11)- VCmab(day 11))/ Vvehicle(day 11) x 100.
