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. 2024 Mar 2;8:60. doi: 10.1038/s41698-024-00557-2

Fig. 8. Mechanism of osimertinib resistance in EGFR-mutated lung cancer with coexisting TP53-GOF mutations.

Fig. 8

Osimertinib treatment induces p65 activation, whereas TP53-GOF mutations promote formation of a p53-p65 complex that binds to the TNF promoter region and thereby increases TNF-α production in osimertinib-treated cells. TNF-α then not only promotes formation and nuclear translocation of the p53-p65 complex but also activates ERK and c-Myc, giving rise to osimertinib resistance. The anti-TNF-α antibody infliximab inhibits TNF-α signaling and thereby suppresses osimertinib resistance.