Fig. 2. TP53-GOF mutation promotes the early development of osimertinib resistance in EGFR-mutant NSCLC cells.

a Time course of PC9/p53^EV, PC9/p53^WT, and PC9/p53^MUT cell number during treatment with 1 μM osimertinib for up to 28 days. b Time course for the development of osimertinib resistance in PC9/p53^EV, PC9/p53^WT, and PC9/p53^MUT cells. The concentration of osimertinib was gradually increased from 10 nM to 1 μM each time the cells achieved 70% confluence. Immunoblot analysis of EGFR signaling as well as of p53 and p21 during treatment with 1 μM osimertinib for up to 72 h for osimertinib-resistant PC9/p53^GOF cells (c) and PC9/p53^EV and PC9/p53^WT cells that had been previously treated with osimertinib for 30 days (d). Data in (a) and (b) are means ± SEM for triplicates from one experiment and are representative of two independent experiments.