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REVIEW

Ferroptosis: Mechanisms, Comparison with Cuproptosis and Emerging Horizons in Therapeutics

Shujie Yin1, Zong Li1, Wen-Bin Ou1,2,*
1 Department of Biopharmaceutics, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
2 Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
* Corresponding Author: Wen-Bin Ou. Email: email
(This article belongs to the Special Issue: The Evolving Landscape of Cancer Treatment: Molecular Insights and Immunotherapeutic Breakthroughs)

Oncology Research https://doi.org/10.32604/or.2025.069049

Received 13 June 2025; Accepted 20 August 2025; Published online 25 September 2025

Abstract

Ferroptosis is an iron-dependent, excessive lipid peroxidation-driven form of regulated cell death. The core mechanisms of ferroptosis include lipid peroxidation cascade, System Xc−-glutathioneglutathione peroxidase 4 axis, iron and lipid metabolism chaos, the NAD(P)Hferroptosis suppressor protein 1—ubiquinone axis, and GTP cyclohydrolase 1 tetrahydrobiopterin-dihydrofolate reductase axis. Cuproptosis is triggered by copper ions and involves ferredoxin 1-mediated aggregation of lipoylated proteins, differing fundamentally from ferroptosis. Both ferroptosis and cuproptosis exhibit dual roles (promote or inhibit) in cancers. And the sensitivity of different cancer types to ferroptosis varies, which may depend on special metabolic signatures (e.g., E-cadherin loss causes epithelial–mesenchymal transition, making tumors gain resistance to ferroptosis) and expression of antioxidant defense regulators (e.g., high expression of Acyl-CoA synthetase long-chain family member 4 and lncFASA make tumors easily sensitive). At present, traditional Chinese herbal medicine, combination therapy, and nano-delivery technology correlated with ferroptosis are being hotly studied by researchers in order to realize clinical translation of ferroptosis. In this review, we have summarized the core mechanisms of ferroptosis, ferroptosis differences from cuproptosis, its impact on cancers, and its translational implications in cancer therapy, helping readers quickly get the new information and horizons on them.

Graphical Abstract

Ferroptosis: Mechanisms, Comparison with Cuproptosis and Emerging Horizons in Therapeutics

Keywords

Ferroptosis; cuproptosis; therapy; cancers

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