Fig. 6. Inhibition of TNF-α signaling suppresses the development of resistance and restores sensitivity to osimertinib in TP53-GOF mutant cells.

Percentage cell number for PC9/p53^GOF mutant cells (a) as well as PC9/p53^EV, PC9/p53^WT, and PC9/p53^V218del cells (b) treated with 1 μM osimertinib (Osi) in the absence or presence of infliximab (1 µg/ml) for the indicated times. Viability of osimertinib-resistant PC9/p53^R248Q (c) and PC9/p53^R273H (d) cells treated with the indicated concentrations of osimertinib in the absence or presence of infliximab (1 µg/ml) for 72 h as measured by a colorimetric assay. e Immunoblot analysis of EGFR signaling as well as p53 and c-Myc expression in osimertinib-resistant PC9/p53^GOF mutant cells incubated in the absence or presence of osimertinib (100 nM) or infliximab (1 µg/ml) for 24 h. Data in (a) through (d) are means ± SEM of triplicates from one experiment and are representative of three independent experiments.