NFE2L2 and cancer: Consistent with this observation, at least five additional mechanisms are known to activate NRF2 in cancer: hypomethylation of KEAP1, accumulation of disruptor proteins, increased production of NRF2, electrophoretic attack of KEAP1 by oncometabolites, and down-regulation of NRF2-targeting microRNAs (miRNAs) [18].