NFE2L2 and cancer: In addition to somatic mutations in NRF2 and KEAP1, several molecular mechanisms have been elucidated for NRF2 overactivation in cancers, including KEAP1 silencing through promoter methylation86, transcriptional NRF2 activation by oncogenes such as KRAS87, NRF2 stabilization by p62 accumulation88, and NRF2 activation by the oncometabolite fumarate89.