Several studies have demonstrated that KEAP1/NRF2 signaling plays an essential role in tumor cell sensitivity to chemotherapy, because NRF2 activation or KEAP1 dysfunction caused by deletion or epigenetic modifications increases resistance to CDDP, particularly in LUAD, in which genes involved in the KEAP1/NEF2 pathway are mutated in 22% of patients.55, 56, 57 Notably, the A549 cell line, which is widely used in lung tumor research, is characterized by a loss-of-function mutation at G333C. The gene discussed is KEAP1; the disease is neoplasm.