KEAP1 and cancer: For example, somatic mutations in KEAP1 and/or NRF2 genes, exon skipping in the NRF2 genome, methylation/demethylation of the KEAP1 promoter, accumulation of p62/sequestosome-1, and mutation of fumarate hydrolase have been reported [60,61] Constitutively activated NRF2 promoted cell proliferation through metabolic changes; inhibiting apoptosis; promoting angiogenesis, and invasion/metastasis; and promoting drug resistance in various cancers has also been reported [62,63].