# Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition

Source: https://onco.cc/key-papers/paper-hangauer-nature/  
OnCo record `paper-hangauer-nature` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one idea page, indexed on Europe PMC as PubMed record 29088702 and published in Nature; the citing page links this DOI, which is how the record was matched.

## Summary

Acquired drug resistance prevents cancer therapies from achieving stable and complete responses. Emerging evidence implicates a key role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. The persister cell pool constitutes a reservoir from which drug-resistant tumours may emerge. Targeting persister cells therefore presents a therapeutic opportunity to impede tumour relapse. We previously found that cancer cells in a high mesenchymal therapy-resistant cell state are dependent on the lipid hydroperoxidase GPX4 for survival. Here we show that a similar therapy-resistant cell state underlies the behaviour of persister cells derived from a wide range of cancers and drug treatments. Consequently, we demonstrate that persister cells acquire a dependency on GPX4. Loss of GPX4 function results in selective persister cell ferroptotic death in vitro and prevents tumour relapse in mice. These findings suggest that targeting of GPX4 may represent a therapeutic strategy to prevent acquired drug resistance.

Indexed on Europe PMC as PubMed record 29088702 (DOI 10.1038/nature24297). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Nature
- Year: 2017
- DOI: 10.1038/nature24297
- Authors: Hangauer MJ, Viswanathan VS, Ryan MJ, et al.
- What it means: One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Nature 2017: https://doi.org/10.1038/nature24297
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29088702/
- Europe PMC: https://europepmc.org/article/MED/29088702

## Connected records

- ideas: [Kill drug-tolerant persisters through ferroptosis](https://onco.cc/ideas/idea-ferroptosis-persisters/)
- journals: [Nature](https://onco.cc/journals/nature/)

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