Persister cancer cells: Iron addiction and vulnerability to ferroptosis

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...

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Bibliographic Details
Published in:Molecular cell Vol. 82; no. 4; p. 728
Main Authors: Rodriguez, Raphaël, Schreiber, Stuart L, Conrad, Marcus
Format: Journal Article
Language:English
Published: United States 17.02.2022
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ISSN:1097-4164, 1097-4164
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Summary: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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ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2021.12.001