ArticleMolecular and cellular biology2021
NRF2-Dependent Bioactivation of Mitomycin C as a Novel Strategy To Target KEAP1-NRF2 Pathway Activation in Human Cancer.
Article in Molecular and cellular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Systemic activation of NRF2 contributes to the therapeutic efficacy of clinically-approved KRAS-G12C anti-cancer drugs.British journal of cancer · 2025Article
- Cisplatin-induced genetic alterations in KEAP1 promote therapeutic resistance in head and neck squamous cell carcinoma.Redox biology · 2025Article
- Phytoconstituents in photoaging: therapeutic potential in prevention and regeneration.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2025Review
- NRF2 activation in cancer and overview of NRF2 small molecule inhibitors.Archives of pharmacal research · 2025Review
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- The Central Role of Cytochrome P450 Reductase (CPR) in Hyperoxic Lung Injury.Expert opinion on drug metabolism & toxicology · 2025Review
- Reactive Oxygen Species: From Tumorigenesis to Therapeutic Strategies in Cancer.Cancer medicine · 2025Review
- The Role of Changes in the Redox Status in the Pathogenesis of Chronic Lymphocytic Leukemia.Doklady. Biochemistry and biophysics · 2024Review
- Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry.Journal of medicinal chemistry · 2024Review
- The role of Keap1-Nrf2 signaling pathway in the treatment of respiratory diseases and the research progress on targeted drugs.Heliyon · 2024Review
- Redefining bioactive small molecules from microbial metabolites as revolutionary anticancer agents.Cancer gene therapy · 2024Review
- Regulation of the Nrf2/HO-1 axis by mesenchymal stem cells-derived extracellular vesicles: implications for disease treatment.Frontiers in cell and developmental biology · 2024Review
- Molecular Basis of the KEAP1-NRF2 Signaling Pathway.Molecules and cells · 2023Review
- Review
- Protein Phosphorylation and Redox Status: An as Yet Elusive Dyad in Chronic Lymphocytic Leukemia.Cancers · 2022Review
- The KEAP1-NRF2 System and Esophageal Cancer.Cancers · 2022Review
- Multifaceted Roles of the KEAP1-NRF2 System in Cancer and Inflammatory Disease Milieu.Antioxidants (Basel, Switzerland) · 2022Review
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- Overview of Ferroptosis and Synthetic Lethality Strategies.International journal of molecular sciences · 2021Review
- The diverse functionality of NQO1 and its roles in redox control.Redox biology · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating mutations in the KEAP1-NRF2 pathway are found in approximately 25% of lung tumors, where the hijacking of NRF2's cytoprotective functions results in aggressive tumor growth, chemoresistance, and a poor prognosis for patients. There are currently no approved drugs which target aberrant NRF2 activation, which means that there is an urgent clinical need to target this orphan oncogenic pathway in human tumors. In this study, we used an isogenic pair of wild-type and Keap1 knockout cells to screen a range of chemotherapeutic and pathway-targeted anticancer drugs in order to identify compounds which display enhanced toxicity toward cells with high levels of Nrf2 activity. Through this approach, complemented by validation across a panel of eight human cancer cell lines from a range of different tissues, we identified the DNA-damaging agent mitomycin C to be significantly more toxic in cells with aberrant Nrf2 activation. Mechanistically, we found that the NRF2 target genes for cytochrome P450 reductase, NQO1, and enzymes in the pentose phosphate pathway are all responsible for the NRF2-dependent enhanced bioactivation of mitomycin C. As mitomycin C is already approved for clinical use, it represents as excellent drug repositioning candidate to target the currently untreatable NRF2 activation in human tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.