Fig. 7. Inhibition of TNF-α signaling suppresses the development of resistance and restores sensitivity to osimertinib in a xenograft mouse model.
a Time course of changes in tumor volume for subcutaneous tumors formed by PC9/p53EV or PC9/p53R248Q cells in nude mice and treated with vehicle or osimertinib (Osi) beginning at day 0 (corresponding to 10 days after cell injection). b Tumors isolated from mice in (a) at day 30. Scale bar, 30 mm. c Time course of changes in tumor volume for subcutaneous tumors formed by PC9/p53R248Q cells in nude mice and treated with vehicle, osimertinib, infliximab, or the combination of osimertinib and infliximab from day 0. Alternatively, infliximab administration was initiated 14 days after the onset of osimertinib treatment. d Tumors isolated from mice in (c) at day 30. Scale bar, 30 mm. For these experiments, osimertinib was administered orally once daily at a dose of 1 mg/kg and infliximab was administered intraperitoneally once a week at a dose of 10 mg/kg. All quantitative data are means ± SEM (n = 5 mice per group). **p < 0.01, ***p < 0.001, ****p < 0.0001 (one-way ANOVA followed by Tukey’s test).