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Ferroptosis\u2014an iron\u2010dependent cell death pathway driven by lipid peroxidation\u2014emerges as a critical regulator of NPC pathobiology. This review synthesizes how ferroptosis suppression promotes NPC tumor growth, metastasis, and therapy resistance. Key mechanisms include: 1. EBV\u2010mediated activation of p62\u2010Keap1\u2010NRF2\/GPX4 and GPX4\u2010TAK1 axes conferring chemo\/radioresistance; 2. Extracellular vesicle (EV)\u2010mediated transfer of ITGB3 or SCARB1 reprogramming tumor\u2010associated macrophages (TAMs) and inhibiting ferroptosis in circulating cells; 3. Metabolic rewiring (e.g., CAPRIN2\/HMGCR, P4HA1\/HMGCS1) enhancing metastasis. Additionally, ferroptosis induction via radiotherapy, natural compounds (solasodine, luteolin), repurposed drugs (disulfiram\/copper), or nanotechnology synergizes with immunotherapy by promoting lipid peroxidation and reversing EBV\u2010mediated immune evasion. Targeting ferroptosis regulators (SLC7A11, GPX4, FTO, CD38) overcomes resistance, positioning ferroptosis modulation as a transformative strategy for NPC management.<\/jats:p>","DOI":"10.1002\/adbi.202500460","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T10:16:34Z","timestamp":1761819394000},"source":"Crossref","is-referenced-by-count":3,"title":["Targeting Ferroptosis in Nasopharyngeal Carcinoma: Mechanisms of Therapy Resistance and Therapeutic Opportunities"],"prefix":"10.1002","volume":"9","author":[{"given":"Dayuan","family":"Zheng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine &amp; Faculty of Chinese Medicine Macau University of Science and Technology  Macau SAR 999078 China"},{"name":"Zhuhai MUST Science and Technology Research Institute Macau University of Science and Technology Hengqin Guangdong\u2010Macao In\u2010Depth Cooperation Zone  Guangdong 519099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Chu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine &amp; 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