KEAP1 and cancer: Apart from mutations in KEAP1, NRF2, and CUL3, NRF2 overactivation in cancer is also caused by epigenetic silencing of KEAP1, NFE2L2 gene amplification, alternative splicing of NFE2L2 mRNA, increase in NRF2 expression by oncoproteins, KEAP1 cysteine modifications by oncometabolites, and binding of competitive protein interactors to KEAP1 or NRF2 [23].