SynthesisFrontiers in oncology2026
Ferroptosis in chemotherapy resistance and resensitization in breast cancer: a systematic review of preclinical evidence and translational implications.
Synthesis in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Chemotherapy resistance remains a major obstacle in breast cancer treatment, particularly in triple-negative breast cancer (TNBC). Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a potential therapeutic vulnerability in drug-resistant cancers, but preclinical evidence lacks systematic synthesis. Methods: PubMed, Scopus, Embase and Web of Science were systematically searched for original studies published between January 2016 and May 2026 investigating ferroptosis in chemotherapy-resistant breast cancer models. Study characteristics, mechanistic data, and outcomes were extracted. Methodological quality was assessed using SYRCLE ( Results: Forty-four studies met inclusion criteria, with the majority published since 2024. TNBC was the focus of 47.7% of studies. Mechanisms were classified into six categories: GPX4 axis (28 studies, 63.6%), iron metabolism regulation (8 studies, 18.2%), SLC7A11/xCT pathway (5 studies, 11.4%), and three single-study mechanisms (6.8% combined). GPX4 modulation demonstrated efficacy across all drug classes. Evidence ranking classified the GPX4 axis, iron metabolism regulation, and the SLC7A11/xCT pathway as Level A (strong evidence), and the remaining mechanisms as Level C. Methodological quality was adequate: 88.6% performed rescue experiments, 79.5% included Conclusion: Ferroptosis regulation represents a mechanistically diverse and promising strategy to overcome breast cancer chemoresistance. The GPX4 axis, iron metabolism regulation, and the SLC7A11/xCT pathway are the most consistently supported mechanisms, providing a framework for prioritizing translational targets. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261334827.
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