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Rodriguez, R.* ; Schreiber, S.L.* ; Conrad, M.

Persister cancer cells: Iron addiction and vulnerability to ferroptosis.

Mol. Cell 82, 728-740 (2022)
Publ. Version/Full Text Postprint DOI PMC
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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
Keywords Glutathione-peroxidase 4; Cystine/glutamate Antiporter; Promotes Ferroptosis; Lipid-peroxidation; Oxidative Stress; Stem-cells; Death; Inhibition; Mechanism; Complex
Language english
Publication Year 2022
Prepublished in Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Journal Molecular Cell
Quellenangaben Volume: 82, Issue: 4, Pages: 728-740 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
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
Scopus ID 85124570769
PubMed ID 34965379
Erfassungsdatum 2022-01-21