Decoding ferroptosis for cancer therapy.
    
    
        
    
    
        
        Nat. Rev. Cancer, DOI: 10.1038/s41568-025-00864-1 (2025)
    
    
    
		
		
			
				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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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Review
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        Glutathione-peroxidase 4; Cell-death; Vitamin-e; Oxidative Stress; Lipid-peroxidation; Prostate-cancer; Iron; Selenium; Gpx4; Pathways
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2025
    
 
    
        Prepublished im Jahr 
        0
    
 
    
        HGF-Berichtsjahr
        2025
    
 
    
    
        ISSN (print) / ISBN
        1474-175X
    
 
    
        e-ISSN
        1474-1768
    
 
    
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            Verlag
            Nature Publishing Group
        
 
        
            Verlagsort
            Heidelberger Platz 3, Berlin, 14197, Germany
        
 
	
        
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        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        30203 - Molecular Targets and Therapies
    
 
    
        Forschungsfeld(er)
        Genetics and Epidemiology
    
 
    
        PSP-Element(e)
        G-506900-001
    
 
    
        Förderungen
        European Research Council (ERC) under the European Union
CRC TRR 353
German Federal Ministry of Education and Research (BMBF) FERROPATH
Deutsche Forschungsgemeinschaft (DFG)
    
 
    
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        Erfassungsdatum
        2025-10-14