Figure 6

Therapeutic effects of radiation, selumitinib and savolitinib on xenograft growth delay. (A) Radiation-induced tumor growth delay curves of UW-lung-2, UW-lung-5, UW-lung-16, UW-lung-18 and UW-lung-21. Radiation was given as 2 Gy per fraction for either 5 days or 10 days as indicated. (B) KRAS G12C mutated UW-lung -2 and UW-lung-16 subcutaneous flank xenografts treated with vehicle or selumitinib 25 mg/kg BID for 10 days. (C) Immunohistochemistry of UW-lung-2 and UW-lung-16 tumor sections showing modulation of KRAS-downstream signaling (p-Erk and p-S6) following a one-time dose of 25 mg/kg BID of selumitnib, collected at 24 h. (D) MET exon 14 mutated UW-lung-21 subcutaneous flank xenografts treated with vehicle, savolitinib 2.5 mg/kg, radiation or radiation plus savolitinib 2.5 mg/kg for 10 days. (E) Immunohistochemistry of UW-lung-21 tumor sections showing modulation of MET signaling (MET, p-MET, p-Erk and p-S6) and decrease in Ki-67 following a single dose of 2.5 mg/kg of savolitinib, collected at 24 h. Points, mean tumor volume in mice after treatment; bars, SEM. The scale bar represents 50 mm and all images are to the same scale.