ArticleBiomolecules2020
High NRF2 Levels Correlate with Poor Prognosis in Colorectal Cancer Patients and with Sensitivity to the Kinase Inhibitor AT9283 In Vitro.
Article in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The trial behind it
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Rewiring redox defense: Nrf2-driven antioxidant signaling as a gateway to programmed cell death activation in colorectal cancer.Genes & diseases · 2027Review
- CUL7-mediated KEAP1 ubiquitination promotes the progression of colon cancer via NRF2 signaling.Cell death & disease · 2026Article
- Multifaceted Anticancer Activity of Flavanone/Chromanone Intermediates for Five-Membered Heterocyclic Derivatives: Targeting Oxidative Stress, Apoptosis, and MAPK Signaling in Colorectal Cancer.Molecules (Basel, Switzerland) · 2026Article
- Reactive oxygen species (ROS) in cancer: from redox signaling and metabolic plasticity to therapeutic vulnerabilities.Exploration of targeted anti-tumor therapy · 2026Review
- The role of NR2F2 in cancer (Review).Oncology letters · 2025Review
- HIPK2 in Colon Cancer: A Potential Biomarker for Tumor Progression and Response to Therapies.International journal of molecular sciences · 2024Review
- Modulators of the Nrf2 Signaling Pathway Enhance the Cytotoxic Effect of Standard Chemotherapeutic Drugs on Organoids of Metastatic Colorectal Cancer.Bulletin of experimental biology and medicine · 2024Article
- The Dual Role of NRF2 in Colorectal Cancer: Targeting NRF2 as a Potential Therapeutic Approach.Journal of inflammation research · 2024Review
- Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers.OncoTargets and therapy · 2024Review
- Small molecule drug discovery for glioblastoma treatment based on bioinformatics and cheminformatics approaches.Frontiers in pharmacology · 2024Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- Electrophilic reactive aldehydes as a therapeutic target in colorectal cancer prevention and treatment.Oncogene · 2023Article
- Terminators or Guardians? Design, Synthesis, and Cytotoxicity Profiling of Chalcone-Sulfonamide Hybrids.ACS omega · 2023Article
- NRF2 and Bip Interconnection Mediates Resistance to the Organometallic Ruthenium-Cymene Bisdemethoxycurcumin Complex Cytotoxicity in Colon Cancer Cells.Biomedicines · 2023Article
- The Aurora kinase inhibitor AT9283 inhibits Burkitt lymphoma growth by regulating Warburg effect.PeerJ · 2023Article
- Genetic alterations of Keap1 confers chemotherapeutic resistance through functional activation of Nrf2 and Notch pathway in head and neck squamous cell carcinoma.Cell death & disease · 2022Article
- The Impact of NRF2 Inhibition on Drug-Induced Colon Cancer Cell Death and p53 Activity: A Pilot Study.Biomolecules · 2022Article
- Pirin, an Nrf2-Regulated Protein, Is Overexpressed in Human Colorectal Tumors.Antioxidants (Basel, Switzerland) · 2022Article
- Nrf2 activation does not affect adenoma development in a mouse model of colorectal cancer.Communications biology · 2021Article
- NRF2 Mediates Therapeutic Resistance to Chemoradiation in Colorectal Cancer through a Metabolic Switch.Antioxidants (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
Aberrant hyperactivation of nuclear factor erythroid 2 (NF-E2) p45-related factor 2 (NRF2) is a common event in many tumour types and associates with resistance to therapy and poor patient prognosis; however, its relevance in colorectal tumours is not well-established. Measuring the expression of surrogate genes for NRF2 activity in silico, in combination with validation in patients' samples, we show that the NRF2 pathway is upregulated in colorectal tumours and that high levels of nuclear NRF2 correlate with a poor patient prognosis. These results highlight the need to overcome the protection provided by NRF2 and present an opportunity to selectively kill cancer cells with hyperactive NRF2. Exploiting the CRISPR/Cas9 technology, we generated colorectal cancer cell lines with hyperactive NRF2 and used them to perform a drug screen. We identified AT9283, an Aurora kinase inhibitor, for its selectivity towards killing cancer cells with hyperactive NRF2 as a consequence to either genetic or pharmacological activation. Our results show that hyperactivation of NRF2 in colorectal cancer cells might present a vulnerability that could potentially be therapeutically exploited by using the Aurora kinase inhibitor AT9283.
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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.