The article "The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?" by Christophe Glorieux et al. explores the complex roles of the nuclear factor erythroid 2-related factor 2 (NRF2) in cancer. NRF2 is a critical transcription factor that regulates cellular antioxidant systems in response to oxidative stress by controlling the expression of genes encoding antioxidant enzymes. The authors discuss the dual nature of NRF2, which can either protect cells from oxidative damage or promote tumor progression, chemotherapy resistance, and metastasis. NRF2 is activated under oxidative stress by dissociating from its negative regulator, Kelch-like ECH-associated protein 1 (KEAP1), and translocating to the nucleus to activate target genes. This process involves multiple mechanisms, including the oxidation of KEAP1's redox-sensitive cysteine residues, competition with other proteins for binding to KEAP1, and phosphorylation events. NRF2 regulates a wide range of genes, including those for antioxidant proteins, NADPH-regenerating enzymes, cytoprotective proteins, and phase 1 and phase 2 enzymes. The authors highlight the anti-oncogenic effects of NRF2 in healthy cells, where it induces the expression of cytoprotective genes to eliminate ROS and detoxify carcinogens. However, in cancer cells, constitutive activation of NRF2 can contribute to chemotherapy resistance, tumor metabolism, immune evasion, and metastasis. Mutations in KEAP1 and NRF2 are common in many cancers and are associated with poor prognosis. The article also discusses the role of NRF2 in dysregulating cell proliferation, tumor metabolism, and cell death. NRF2 promotes cancer cell proliferation by activating genes involved in cell growth and proliferation, leading to a "NRF2 addiction" phenotype. In tumor metabolism, NRF2 enhances glutaminolysis, nucleotide metabolism, and the pentose phosphate pathway, contributing to metabolic reprogramming and cell proliferation. NRF2 also plays a role in modulating immune responses and long non-coding RNAs (LncRNAs) in the tumor microenvironment. Overall, the review emphasizes the multifaceted roles of NRF2 in both cancer prevention and promotion, highlighting the need for a better understanding of its mechanisms to develop effective therapeutic strategies.The article "The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?" by Christophe Glorieux et al. explores the complex roles of the nuclear factor erythroid 2-related factor 2 (NRF2) in cancer. NRF2 is a critical transcription factor that regulates cellular antioxidant systems in response to oxidative stress by controlling the expression of genes encoding antioxidant enzymes. The authors discuss the dual nature of NRF2, which can either protect cells from oxidative damage or promote tumor progression, chemotherapy resistance, and metastasis. NRF2 is activated under oxidative stress by dissociating from its negative regulator, Kelch-like ECH-associated protein 1 (KEAP1), and translocating to the nucleus to activate target genes. This process involves multiple mechanisms, including the oxidation of KEAP1's redox-sensitive cysteine residues, competition with other proteins for binding to KEAP1, and phosphorylation events. NRF2 regulates a wide range of genes, including those for antioxidant proteins, NADPH-regenerating enzymes, cytoprotective proteins, and phase 1 and phase 2 enzymes. The authors highlight the anti-oncogenic effects of NRF2 in healthy cells, where it induces the expression of cytoprotective genes to eliminate ROS and detoxify carcinogens. However, in cancer cells, constitutive activation of NRF2 can contribute to chemotherapy resistance, tumor metabolism, immune evasion, and metastasis. Mutations in KEAP1 and NRF2 are common in many cancers and are associated with poor prognosis. The article also discusses the role of NRF2 in dysregulating cell proliferation, tumor metabolism, and cell death. NRF2 promotes cancer cell proliferation by activating genes involved in cell growth and proliferation, leading to a "NRF2 addiction" phenotype. In tumor metabolism, NRF2 enhances glutaminolysis, nucleotide metabolism, and the pentose phosphate pathway, contributing to metabolic reprogramming and cell proliferation. NRF2 also plays a role in modulating immune responses and long non-coding RNAs (LncRNAs) in the tumor microenvironment. Overall, the review emphasizes the multifaceted roles of NRF2 in both cancer prevention and promotion, highlighting the need for a better understanding of its mechanisms to develop effective therapeutic strategies.