KEAP1 and cancer: There are several mechanisms by which Nrf2 signaling pathway is constitutively activated in cancer cells: (1) somatic mutations in Keap1 or the Keap1 binding domain, that disrupt binding of Nrf2 and Keap1; (2) epigenetic silencing of Keap1; (3) accumulation of disruptor proteins such as p62, which leads to the dissociation of the Nrf2-Keap1 complex; (4) transcriptional induction of Nrf2 by oncogenic K-Ras, B-Raf and, c-Myc; and (5) post-translational modification of Keap1 cysteines by succinylation [4,5,6,7,8,9,10,11].