KRAS/BRAF WT Tumor PDX Models

PDX experiments were performed as previously described^{59 (link)}. Basically, four KRAS/BRAF WT PDX lines were selected. Patient-derived tumor tissues were cut into small fragments (3 mm³) and subcutaneously implanted into immunocompromised mice (GemPharmatech Co., Ltd.). For single drug treatment, when tumor volume reached ~50 mm³, mice were randomly allocated to two groups and were i.p. injected with either cetuximab (40 mg/kg, Selleck) or vehicle once a week. For combination treatment, when tumor volume reached ~50 mm³, mice were randomly allocated to the following treatment groups: (1) vehicle control; (2) cetuximab (40 mg/kg, Selleck); (3) LGK974 (3 mg/kg, Apexbio), (4) cetuximab and LGK974 using doses described above. Administration of cetuximab was the same as addressed above. LGK974 was administered to mice via i.p. injection every day. Mouse weights and tumor volumes were measured every three days during the experiments.