However, sustained Nrf2 activation by impairment in autophagy and increase in p62 phosphorylation promotes antineoplastic drug chemoresistance as well as cancer cell proliferation, whereas mutation in KIR domain in p62, which prevents Keap1-p62 interaction, is associated with an ROS increase [42,44,48,49,50,51]. This evidence concerns the gene KEAP1 and cancer.