Details

Autor(en) / Beteiligte

• Rodriguez, Raphaël
• Schreiber, Stuart L.
• Conrad, Marcus

Titel

Persister cancer cells: Iron addiction and vulnerability to ferroptosis

Ist Teil von

• Molecular cell, 2022-02, Vol.82 (4), p.728-740

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. Rodriguez et al. discuss how iron allows cells to acquire a drug-tolerant persister cancer state and how this addiction confers a high vulnerability to ferroptosis. This feature therefore opens up unprecedented opportunities to identify new predictors of ferroptosis sensitivity and provides the basis for the development of next-generation therapeutics.