Fig. 8: Mechanism of osimertinib resistance in EGFR-mutated lung cancer with coexisting TP53-GOF mutations. | npj Precision Oncology

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

From: TP53 gain-of-function mutations promote osimertinib resistance via TNF-α–NF-κB signaling in EGFR-mutated lung cancer

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.

Back to article page