# Ferroptosis & regulated cell death

Source: https://onco.cc/pathways/ferroptosis-cell-death/  
OnCo record `ferroptosis-cell-death` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cells can die in several programmed ways. Beyond the classic apoptosis, ferroptosis kills through iron-driven fat oxidation, and drug-resistant, mesenchymal cancer cells turn out to be unusually prone to it.

## Summary

Ferroptosis is iron-dependent lipid peroxidation restrained by GPX4 (using glutathione from the cystine transporter SLC7A11/xCT) and by FSP1. Therapy-persistent, mesenchymal, and dedifferentiated cancer cells depend on GPX4; radiation and some immunotherapies act partly via ferroptosis. Necroptosis (RIPK3/MLKL) and pyroptosis (gasdermins) are inflammatory death modes that can be immunogenic. No ferroptosis inducer is approved; GPX4 inhibitors lack drug-like properties, so xCT inhibition, cyst(e)inase, and sulfasalazine repurposing are the clinical routes.

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- Analogy: Ferroptosis is rust. Iron plus oxygen eats through the cell's membranes unless an antioxidant crew (GPX4) keeps repainting them. Cells that changed shape to dodge chemotherapy have thinner paint.
- Interventions: xCT inhibitors, cyst(e)inase, sulfasalazine repurposing (early trials); Radiotherapy and IFN-γ from T cells induce lipid peroxidation; BH3 mimetics (venetoclax) exploit apoptosis; MCL-1 inhibitors in development; Persister-cell targeting after EGFR/ALK inhibitors (preclinical)

## Notes

- Leading programmes: Stockwell (Columbia, coined ferroptosis); Dixon (Stanford); Schreiber (Broad) on persister-cell GPX4 dependence; Jiang (MSK) on ferroptosis in immunotherapy.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Ferroptosis
- Stockwell, Ferroptosis turns 10 (Cell 2022): https://doi.org/10.1016/j.cell.2022.06.003
- Viswanathan et al., Dependency of a therapy-resistant state on a lipid peroxidase pathway (Nature 2017): https://doi.org/10.1038/nature23007

## Connected records

- targets: [BCL-2](https://onco.cc/targets/bcl2/)
- drugs: [Venetoclax](https://onco.cc/drugs/venetoclax/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/), [Stanford Health Care / Stanford Cancer Institute](https://onco.cc/institutions/stanford/)
- pathways: [Cancer metabolism](https://onco.cc/pathways/cancer-metabolism/), [Drug-tolerant persister cells](https://onco.cc/pathways/drug-tolerant-persisters/), [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/), [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/), [KEAP1-NRF2 antioxidant pathway](https://onco.cc/pathways/keap1-nrf2/), [Lipid synthesis, uptake & cholesterol](https://onco.cc/pathways/lipid-metabolism-cancer/)
- terms: [Apoptosis](https://onco.cc/terms/apoptosis/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Hallmark: resisting cell death](https://onco.cc/terms/resisting-cell-death/)
- key papers: [Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway](https://onco.cc/key-papers/paper-viswanathan-nature/), [Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications](https://onco.cc/key-papers/paper-stockwell-cell/)
- ideas: [Kill drug-tolerant persisters through ferroptosis](https://onco.cc/ideas/idea-ferroptosis-persisters/)

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