{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:50Z","timestamp":1788415970842,"version":"build-2803163510"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Ferroptosis, an iron-dependent form of regulated cell death, is increasingly recognized as a context-dependent therapeutic vulnerability in cancer, particularly as malignant cells adapt to oxidative, metabolic, and therapy-induced stresses. As a prevalent and reversible epitranscriptomic modification, RNA N6-methyladenosine (m6A) modification orchestrates RNA stability, translation, splicing and decay; consequently, its dysregulation contributes to cancer progression and therapeutic resistance. The intersection of m6A regulation and ferroptosis is therefore biologically important because many ferroptosis threshold genes are short-lived, stress-responsive transcripts controlled by writers, erasers, readers and RNA-binding proteins. This review synthesizes empirical evidence elucidating how m6A regulators remodel cystine import, GPX4-dependent antioxidant defense, FSP1 signaling, lipid metabolism, iron handling, autophagy and tumor-microenvironmental communication. We organize the evidence by regulatory layer rather than cancer type, covering writer-mediated deposition, reader and RNA-binding protein recognition, eraser-dependent demethylation, non-coding RNA and exosomal regulation, and downstream ferroptosis modules. We further discuss how this axis contributes to radiotherapy, chemotherapy, targeted-therapy resistance and ferroptosis-sensitizing combinations. Although m6A-ferroptosis crosstalk offers promising biomarker and therapeutic opportunities, translation requires transcript-level validation, standardized ferroptosis assays, tumor-selective delivery and clinically meaningful patient stratification. A deeper and more precise integration of epitranscriptomics with ferroptosis biology holds the potential to transform stress-adaptive RNA circuits into actionable vulnerabilities for precision cancer therapy.<\/jats:p>","DOI":"10.3389\/fcell.2026.1928071","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:16:22Z","timestamp":1788412582000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["RNA m6A modification-regulated ferroptosis in cancer: mechanism and therapeutic potential"],"prefix":"10.3389","volume":"14","author":[{"given":"Qingmiao","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangni","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Practice, The First Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaonan","family":"Guan","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.immuni.2024.03.019","article-title":"Ironing out the role of ferroptosis in immunity","volume":"57","author":"Bell","year":"2024","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/s41586-019-1705-2","article-title":"The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis","volume":"575","author":"Bersuker","year":"2019","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"217004","DOI":"10.1016\/j.canlet.2024.217004","article-title":"m(6)A modification of lncRNA ABHD11-AS1 promotes colorectal cancer progression and inhibits ferroptosis through TRIM21\/IGF2BP2\/FOXM1 positive feedback loop","volume":"596","author":"Bian","year":"2024","journal-title":"Cancer Lett."},{"key":"B4","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12943-024-02089-6","article-title":"Writers, readers, and erasers RNA modifications and drug resistance in cancer","volume":"23","author":"Chen","year":"2024","journal-title":"Mol. 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