The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) pathway is one of the major signaling cascades involved in cell defense and survival against endogenous and exogenous stress. While Nrf2 and its target genes provide protection against various age-related diseases including tumorigenesis, constitutively active Nrf2 in cancer cells increases the expression of cytoprotective genes and, consequently, enhances proliferation via metabolic reprogramming and inhibition of apoptosis. Herein, we review the current understanding of the regulation of Nrf2 in normal cells as well as its dual role in cancer. Furthermore, the mechanisms of Nrf2 dysregulation in cancer, consequences of unchecked Nrf2 activity, and therapies targeting the Keap1-Nrf2 system are discussed.
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