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Nrf-Mediated Autophagy and Upr: Exploring New Avenues to Overcome Cancer Chemo-Resistance Publisher Pubmed



Dastghaib S1 ; Shafiee SM2 ; Ramezani F3 ; Ashtari N4 ; Tabasi F5 ; Saffarichaleshtori J6, 7 ; Siri M8 ; Vakili O8, 9 ; Igder S10 ; Zamani M8 ; Niknam M2 ; Nasery MM11 ; Kokabi F12 ; Wiechec E13, 14, 17 Show All Authors
Authors
  1. Dastghaib S1
  2. Shafiee SM2
  3. Ramezani F3
  4. Ashtari N4
  5. Tabasi F5
  6. Saffarichaleshtori J6, 7
  7. Siri M8
  8. Vakili O8, 9
  9. Igder S10
  10. Zamani M8
  11. Niknam M2
  12. Nasery MM11
  13. Kokabi F12
  14. Wiechec E13, 14, 17
  15. Mostafavipour Z6, 8
  16. Mokarram P2
  17. Ghavami S4, 14, 15, 16
Show Affiliations
Authors Affiliations
  1. 1. Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, 7193635899, Iran
  2. 2. Autophagy Research Center, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 7134845794, Iran
  3. 3. Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, 51664, Iran
  4. 4. Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, R3E 0J9, MB, Canada
  5. 5. Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, 52242, IA, United States
  6. 6. Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 7134845794, Iran
  7. 7. Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, 8813833435, Iran
  8. 8. Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, 7134845794, Iran
  9. 9. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 73461-81746, Iran
  10. 10. Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 6135715794, Iran
  11. 11. Nanomedicine Research Association (NRA), Universal Scientific Education and Research Network (USERN), Tehran, 7616911319, Iran
  12. 12. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran
  13. 13. Division of Cell Biology, Department of Biomedical and Clinical Sciences, Linkoping University, Linkoping, Sweden
  14. 14. Academy of Silesia, Faculty of Medicine, Rolna 43, Katowice, 40-555, Poland
  15. 15. Research Institutes of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, R3E 0V9, MB, Canada
  16. 16. Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, R3E 0V9, MB, Canada
  17. 17. Department of Otorhinolaryngology in Linkoping, Anaesthetics, Operations and Specialty Surgery Center, Region Ostergotland, Linkoping, 58185, Sweden

Source: European Journal of Pharmacology Published:2025


Abstract

The development of chemo-resistance remains a significant hurdle in effective cancer therapy. NRF1 and NRF2, key regulators of redox homeostasis, play crucial roles in the cellular response to oxidative stress, with implications for both tumor growth and resistance to chemotherapy. This study delves into the dualistic role of NRF2, exploring its protective functions in normal cells and its paradoxical support of tumor survival and drug resistance in cancerous cells. We investigate the interplay between the PERK/NRF signaling pathway, ER stress, autophagy, and the unfolded protein response, offering a mechanistic perspective on how these processes contribute to chemoresistance. Our findings suggest that targeting NRF signaling pathways may offer new avenues for overcoming resistance to chemotherapeutic agents, highlighting the importance of a nuanced approach to redox regulation in cancer treatment. This research provides a molecular basis for the development of NRF-targeted therapies, potentially enhancing the efficacy of existing cancer treatments and offering hope for more effective management of resistant tumors. © 2024 The Authors
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