Fig. 5
Aderbasib restores the antitumor activity of PEPDG278D by inhibiting HB-EGF shedding. a Mice bearing subcutaneous tumors were randomized to EP treatment (n = 12–16), aderbasib treatment (n = 12), or treatment with EP plus aderbasib and PEPDG278D (n = 12). Mice were treated with EP daily (HCT116 tumors: days 2–17; HT29 tumors: days 3–17), aderbasib daily (HCT116 tumors: days 4–17; HT29 tumors: days 4–17), and PEPDG278D thrice weekly (HCT116 tumors: days 5–17; HT29 tumors: days 5–17). EP and PEPDG278D were administered to mice by ip at 0.5, and 4 mg/kg per dose, respectively. Aderbasib was administered to mice by gavage at 60 mg/kg per dose. Group average tumor sizes were 92–110 mm3 (HCT116 tumors) and 153–172 mm3 (HT29 tumors) at the beginning of treatment. Each value is mean ± SEM. **P < 0.01, ****P < 0.001, by one-way ANOVA, followed by Tukey test. b Tumor levels of soluble HB-EGF. Each value is mean ± SD (n = 3). ****P < 0.0001 by one-way ANOVA, followed by Tukey test. c Western blotting of tumor homogenates (2 tumors per group). Tumors were harvested 24 h after final treatment. See Fig. 1 and Fig. 2 legends for protein phosphorylation sites