{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:04:32Z","timestamp":1791839072639,"version":"4.3.4"},"reference-count":112,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Science and ICT (MSIT), Republic of Korea","doi-asserted-by":"publisher","award":["2019R1A2C2002259"],"award-info":[{"award-number":["2019R1A2C2002259"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Anaplastic thyroid cancer (ATC) is among the most lethal human malignancies, characterized by rapid progression, therapeutic resistance, and a median survival of less than one year. Conventional therapies, including surgery, radiotherapy, and chemotherapy, have limited effect, and targeted or immune-based treatments provide only transient benefit. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has recently emerged as a therapeutic vulnerability in ATC. This review synthesizes current evidence on ferroptosis biology, preclinical validation, and therapeutic implications in ATC. Genomic alterations such as TP53, BRAFV600E, RAS, and PIK3CA converge on redox imbalance and metabolic rewiring, rendering ATC cells dependent on antioxidant defenses. Dysregulated iron homeostasis through ferritinophagy and HO-1 activity, together with lipid remodeling via ACSL4 and LPCAT3, further sensitizes ATC to ferroptosis. Preclinical studies show that pharmacological inducers, including vitamin C, tenacissoside H, neferine, curcumin, and shikonin, as well as targeted agents such as dabrafenib and anlotinib, can trigger or synergize with ferroptosis. Genetic regulators, including SIRT6, the GPR34\u2013USP8 axis, and the EIF3H\u2013\u03b2-catenin pathway, modulate ferroptosis sensitivity, while RON receptor signaling links glycolysis to ferroptosis resistance. Combination regimens provide further translational potential. Nanoplatforms also offer innovative delivery strategies. Therapeutic approaches include initiating ferroptosis through iron and PUFA enrichment, disabling defenses such as GPX4 and Nrf2, and integrating ferroptosis inducers with existing modalities. Although systemic toxicity and resistance remain obstacles, biomarker-driven selection and drug repurposing offer promise. Ferroptosis represents a mechanistically distinct and clinically exploitable pathway for ATC.<\/jats:p>","DOI":"10.3390\/cells14221800","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:04:07Z","timestamp":1763388247000},"page":"1800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ferroptosis in Anaplastic Thyroid Cancer: Molecular Mechanisms, Preclinical Evidence, and Therapeutic Prospects"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-1756","authenticated-orcid":false,"given":"Jaewang","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam 13496, Republic of Korea"},{"name":"Logsynk, Seoul 11160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1537-1977","authenticated-orcid":false,"given":"Jong-Lyel","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam 13496, Republic of Korea"},{"name":"Department of Biomedical Science, General Graduate School, CHA University, Pocheon 11160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.ecl.2025.03.009","article-title":"Advances in Anaplastic Thyroid Cancer Treatment","volume":"54","author":"Hamidi","year":"2025","journal-title":"Endocrinol. 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