NFE2L2 and cancer: Fumarate can irreversibly modify the cysteine residues in Kelch-like ECH-associated protein 1 (KEAP1) by succination, thereby activating nuclear factor erythroid-2-related factor 2 (NRF2) and promoting a reductive environment supporting cellular proliferation.55 In addition, analysis on a pan-cancer cell line set (from Cancer Cell Line Encyclopedia [CCLE]) has highlighted that mutations in the KEAP1 gene are associated with higher levels of redox metabolites such as glutathione (GSH/GSSG) and NADP+.