{"entity":{"id":"idea-bio1-persister-ferroptosis","kind":"idea","name":"Kill the sleeping survivor cells with iron-dependent cell death","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["synthetic-lethality-approaches"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance","mrd"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-dormancy-mrd"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":6},"route":"/ideas/idea-bio1-persister-ferroptosis/","neighbours":{"technology":[{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}]}}