Nrf2 signaling pathway can be constitutively activated in cancers in several ways including mutations in oncogenic Myc, KRas (Kirsten rat sarcoma) and BRaf (v-raf murine sarcoma viral oncogene homolog B1) via mitogen-activated protein kinases (MAPKs) [142], mutations in Keap1, Cul3, or Nrf2 leading to disruptions in the Keap1/Nrf2 axis [140], and DNA methylation of Keap1 reducing Keap1 expression [143]. This evidence concerns the gene CUL3 and cancer.