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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Abstract 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.
AbstractList 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.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.
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.
Author Conrad, Marcus
Rodriguez, Raphaël
Schreiber, Stuart L
Author_xml – sequence: 1
  givenname: Raphaël
  surname: Rodriguez
  fullname: Rodriguez, Raphaël
  email: raphael.rodriguez@curie.fr
  organization: Chemical Biology of Cancer at Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, Paris, France. Electronic address: raphael.rodriguez@curie.fr
– sequence: 2
  givenname: Stuart L
  surname: Schreiber
  fullname: Schreiber, Stuart L
  email: stuart_schreiber@harvard.edu
  organization: Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: stuart_schreiber@harvard.edu
– sequence: 3
  givenname: Marcus
  surname: Conrad
  fullname: Conrad, Marcus
  email: marcus.conrad@helmholtz-muenchen.de
  organization: Institute of Metabolism and Cell Death, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Pirogov National Research Medical University, Laboratory of Experimental Oncology, Moscow 117997, Russia. Electronic address: marcus.conrad@helmholtz-muenchen.de
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34965379$$D View this record in MEDLINE/PubMed
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Snippet Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to...
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SubjectTerms 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
Title Persister cancer cells: Iron addiction and vulnerability to ferroptosis
URI https://www.ncbi.nlm.nih.gov/pubmed/34965379
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