NFE2L2 and lung adenocarcinoma: Mutations in KEAP1 were first discovered in human lung adenocarcinoma cell lines, wherein a glycine-to-cysteine substitution within the Nrf2-binding domain of Keap1 reduces its affinity for Nrf2, resulting in loss of canonical Nrf2 regulation and constitutive Nrf2 hyperactivation [163].