Fig. 4.

Optimized drug combination efficacy in DLD1 orthotopic in vivo model. a. Tumor weight of DLD1 orthotopic xenografts at the experimental endpoint after 30 days of daily treatment with CTRL (n = 11), ODC (n‐7), 15 mg/kg regorafenib (n = 3), 12.5 mg/kg erlotinib (n = 4), 5 mg/kg selumetinib (n = 4), and 75 mg/kg vemurafenib (n = 3). With an average of 64% inhibition on tumor weight for ODC treatment vs. 100% CTRL, synergy (S) was confirmed based on Bliss independence (64% observed inhibition vs 17% predicted additive activity on tumor weight). b. Mice weight change over time. Standard deviation (SD) increased over time with an average SD in grams of 1.24 for control, 1.24 for ODC, 1.56 for regorafenib, 1.23 for selumetinib, 0.83 for vemurafenib, and 1.84 for erlotinib. c. Representative bioluminescence images of DLD1 tumors at days 0, 14, and 28 of treatment and d. representative images of the DLD1 tumors after resection at the endpoint. Significance of *p < 0.05, **p < 0.01, and ***p < 0.001 represent the comparison of the ODC with all other groups using an unpaired Student’s t‐test (a) or the comparison with no weight loss using a two‐way ANOVA with post hoc Dunnett’s multiple comparisons test (b)