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Wahida, A. ; Conrad, M.

Decoding ferroptosis for cancer therapy.

Nat. Rev. Cancer, DOI: 10.1038/s41568-025-00864-1 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Resisting cell death is a pivotal hallmark of cancer and one of several increasingly actionable functional capabilities acquired by cancer cells to sustain their malignant state. Since the early 2000s, the discovery of multiple regulated cell death programmes has intensified interest in targeting these maladaptive traits that cancer cells employ to resist cellular demise. Among these, ferroptosis - the lethal outcome of iron-dependent (phospho)lipid peroxidation - stands apart from other regulated cell death mechanisms, as it is persistently suppressed while lacking an activating signal. In cancer research, ferroptosis has garnered considerable attention, with growing evidence suggesting that its deregulation intersects with other hallmarks of malignancy, thus positioning it as a pleiotropic target. However, in the absence of approved ferroptosis-based drugs and despite substantial advances in understanding the metabolic manoeuvres of cancer cells to evade ferroptosis, its heralded translational value remains somewhat speculative at this stage. This Review reconciles the biochemical foundation of ferroptosis, the evidence supporting its role in cancer biology and the potential strategies for rationalizing targeted therapies to induce ferroptosis-prone states in malignancies. Building on this foundation, we explore contentious issues surrounding ferroptosis, including its implications for immunogenicity and redox imbalances in cancer. Finally, we address critical considerations such as therapeutic windows and biomarkers of ferroptosis, which are prerequisites for successful translation into clinical oncology.
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Publication type Article: Journal article
Document type Review
Keywords Glutathione-peroxidase 4; Cell-death; Vitamin-e; Oxidative Stress; Lipid-peroxidation; Prostate-cancer; Iron; Selenium; Gpx4; Pathways
ISSN (print) / ISBN 1474-175X
e-ISSN 1474-1768
Journal Nature Reviews - Cancer
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)
Grants European Research Council (ERC) under the European Union
CRC TRR 353
German Federal Ministry of Education and Research (BMBF) FERROPATH
Deutsche Forschungsgemeinschaft (DFG)