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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Veröffentlicht in:Molecular cell Jg. 82; H. 4; S. 728
Hauptverfasser: Rodriguez, Raphaël, Schreiber, Stuart L, Conrad, Marcus
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 17.02.2022
Schlagworte:
Animals
Antineoplastic Agents - therapeutic use
Cell Differentiation
Ferroptosis - drug effects
Homeostasis
Humans
Iron - metabolism
Lipid Peroxidation - drug effects
Molecular Targeted Therapy
Neoplasms - drug therapy
Neoplasms - metabolism
Neoplasms - pathology
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Reactive Oxygen Species - metabolism
Signal Transduction
ISSN:1097-4164, 1097-4164
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
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ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2021.12.001