However, sustained Nrf2 activation by an impairment in autophagy and an increase in p62 phosphorylation promotes antineoplastic drug chemoresistance, as well as cancer cell proliferation, whereas a mutation in the KIR domain in p62, which prevents a Keap1–p62 interaction, is associated with an ROS increase [37,38,39,40,41,42]. This evidence concerns the gene NFE2L2 and cancer.