REVIEW article
Front. Oncol.
Sec. Cancer Genetics
This article is part of the Research TopicMetal-Induced Carcinogenesis: Exploring Genetic and Epigenetic Mechanisms Underpinning Cancer DevelopmentView all articles
Modulating Nrf2 to Control Lipid Peroxidation and Ferroptosis: Implications for Cancer Management
Provisionally accepted
- 1F. Kimya Anabilim Dalı, Ankara Universitesi Eczacilik Fakultesi, Ankara, Türkiye
- 2F. Toksikoloji Anabilim Dalı, Ankara Universitesi Eczacilik Fakultesi, Ankara, Türkiye
- 3Universita degli Studi del Molise Dipartimento di Medicina e Scienze della Salute Vincenzo Tiberio, Campobasso, Italy
- 4Department of Physiology and Pharmacology, Universita degli Studi di Roma La Sapienza, Rome, Italy
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Nuclear factor erythroid 2–related factor 2 (Nrf2) is a key transcription factor that regulates the expression of genes involved in cellular protection against oxidative stress and the maintenance of redox homeostasis. In addition to modulating reactive oxygen species (ROS), Nrf2 influences lipid peroxidation (LP) and ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxide accumulation. Dysregulation of Nrf2 signaling has been implicated in the pathogenesis and progression of several malignancies, where it affects tumor cell survival, chemoresistance, and metabolic reprogramming. This review summarizes current knowledge on the complex relationship between Nrf2 activity, LP dynamics, and ferroptotic mechanisms in cancer biology. It also highlights how Nrf2-dependent transcriptional programs not only regulate antioxidant responses but also contribute to cellular detoxification, metabolism, autophagy, and proteostasis, processes closely linked to tumorigenesis and cancer cell adaptability. Given that Nrf2 may have a dual role in cancer, either promoting cytoprotection or supporting tumor progression and chemoresistance, we discuss emerging strategies to selectively modulate Nrf2 and ferroptosis-related pathways to increase cancer cell sensitivity to oxidative damage and reduce resistance.
Keywords: Nrf2, Nrf2 modulators, Lipid Peroxidation, ferroptosis, Oxidative Stress, Cancer
Received: 08 Sep 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Tunç, Ates, Yilmaz, Medoro, Davinelli, Suzen and Saso. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ilker Ates, ilkerates976@gmail.com
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