# Kill the sleeping survivor cells with iron-dependent cell death

Source: https://onco.cc/ideas/idea-bio1-persister-ferroptosis/  
OnCo record `idea-bio1-persister-ferroptosis` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A few cancer cells survive treatment by going quiet rather than mutating. These survivors are unusually vulnerable to a particular kind of cell death, which a drug could trigger.

## Summary

Drug-tolerant persister cells adopt a mesenchymal, slow-cycling state that depends on the lipid peroxidase GPX4; their elimination by GPX4 inhibition has been shown in several models across lung, breast and other cancers. Translating this requires a tolerable GPX4 inhibitor or an alternative ferroptosis inducer, and a schedule that applies it during the persister window shortly after maximal response.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Ferroptosis induction timed to the persister window after maximal response to targeted therapy reduces residual disease and delays regrowth in vivo compared with continued targeted therapy alone.
- Rationale: Persisters are the reservoir from which genetic resistance later emerges; eliminating them attacks resistance before mutations arise, and the vulnerability is a state rather than a genotype, so it applies across drivers.
- Proposed test: In vivo studies in three driver-defined models comparing scheduled ferroptosis induction at nadir with continuous therapy, measuring residual cell number and time to regrowth.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- technologies: [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/)
- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)

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