EGFR and non-small cell lung carcinoma: With this respect, by establishing Gefitinib-resistant (GR) NSCLC cells, it has been shown that the increased overexpression of several NRF2-dependent target genes was due to an acquired KEAP1 mutation, an event promoting a malignant phenotype and cross-resistance to the EGFR-TKIs Afatinib and Osimertinib both in vitro and in vivo.