Persister cancer cells: Iron addiction and vulnerability to ferroptosis.
    
    
        
    
    
        
        Mol. Cell 82, 728-740 (2022)
    
    
    
      
      
	
	    Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to iron-mediated production of lethal oxygen radicals. This cell death modality has been detected across many organisms, including in mammals, where it can be used as a defense mechanism against pathogens or even harnessed by T cells to sensitize tumor cells toward effective killing. Conversely, ferroptosis is considered one of the main cell death mechanisms promoting degenerative diseases. Emerging evidence suggests that ferroptosis represents a vulnerability in certain cancers. Here, we critically review recent advances linking ferroptosis vulnerabilities of dedifferentiating and persister cancer cells to the dependency of these cells on iron, a potential Achilles heel for small-molecule intervention. We provide a perspective on the mechanisms reliant on iron that contribute to the persister cancer cell state and how this dependency may be exploited for therapeutic benefits.
	
	
	    
	
       
      
	
	    
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Review
    
 
    
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        Keywords
        Glutathione-peroxidase 4; Cystine/glutamate Antiporter; Promotes Ferroptosis; Lipid-peroxidation; Oxidative Stress; Stem-cells; Death; Inhibition; Mechanism; Complex
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2022
    
 
    
        Prepublished in Year
        2021
    
 
    
        HGF-reported in Year
        2021
    
 
    
    
        ISSN (print) / ISBN
        1097-2765
    
 
    
        e-ISSN
        1097-4164
    
 
    
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	    Volume: 82,  
	    Issue: 4,  
	    Pages: 728-740 
	    Article Number: ,  
	    Supplement: ,  
	
    
 
    
        
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            Publisher
            Elsevier
        
 
        
            Publishing Place
            50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30203 - Molecular Targets and Therapies
    
 
    
        Research field(s)
        Genetics and Epidemiology
    
 
    
        PSP Element(s)
        G-506900-001
    
 
    
        Grants
        Else Kroner-Fresenius-Stiftung
Fondation Charles Defforey-Institut de France
Ligue contre le Cancer
Region Ile-de-France
National Cancer Institute's Cancer Target Discovery and Development (CTD2) Network
Deutsche Forschungsgemeinschaft (DFG)
German Federal Ministry of Education and Research (BMBF) VIP+ program NEURO-PROTEKT
Ministry of Science and Higher Education of The Russian Federation
ERC under the European Union's Horizon 2020 research and innovation program
European Research Council (ERC) under the European Union
    
 
    
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        Erfassungsdatum
        2022-01-21