Ferroptosis and head and neck cancer: Mechanisms and therapeutic perspectives (Review)

Chow LQM: Head and neck cancer. N Engl J Med. 382:60–72. 2020. View Article : Google Scholar

Swiecicki PL, Yilmaz E, Rosenberg AJ, Fujisawa T, Bruce JY, Meng C, Wozniak M, Zhao Y, Mihm M, Kaplan J, et al: Phase II trial of enfortumab vedotin in patients with previously treated advanced head and neck cancer. J Clin Oncol. 43:578–588. 2025. View Article : Google Scholar

Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L and Gregoire V: Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 31:1462–1475. 2020. View Article : Google Scholar : PubMed/NCBI

Ruffin AT, Li H, Vujanovic L, Zandberg DP, Ferris RL and Bruno TC: Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment. Nat Rev Cancer. 23:173–188. 2023. View Article : Google Scholar :

Hashim D, Genden E, Posner M, Hashibe M and Boffetta P: Head and neck cancer prevention: From primary prevention to impact of clinicians on reducing burden. Ann Oncol. 30:744–756. 2019. View Article : Google Scholar :

Castelli J, Thariat J, Benezery K, Hasbini A, Gery B, Berger A, Liem X, Guihard S, Chapet S, Thureau S, et al: Weekly adaptive radiotherapy vs. standard Intensity-modulated radiotherapy for improving salivary function in patients with head and neck cancer: A phase 3 randomized clinical trial. JAMA Oncol. 9:1056–1064. 2023. View Article : Google Scholar : PubMed/NCBI

Budach V and Tinhofer I: Novel prognostic clinical factors and biomarkers for outcome prediction in head and neck cancer: A systematic review. Lancet Oncol. 20:e313–e326. 2019. View Article : Google Scholar : PubMed/NCBI

Chen X, Kang R, Kroemer G and Tang D: Broadening horizons: The role of ferroptosis in cancer. Nat Rev Clin Oncol. 18:280–296. 2021. View Article : Google Scholar

Zhou Q, Meng Y, Li D, Yao L, Le J, Liu Y, Sun Y, Zeng F, Chen X and Deng G: Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies. Signal Transduct Target Ther. 9:552024. View Article : Google Scholar : PubMed/NCBI

Lei G, Zhuang L and Gan B: The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions. Cancer Cell. 42:513–534. 2024. View Article : Google Scholar : PubMed/NCBI

Lei G, Zhuang L and Gan B: Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer. 22:381–396. 2022. View Article : Google Scholar

Mou Y, Wang J, Wu J, He D, Zhang C, Duan C and Li B: Ferroptosis, a new form of cell death: Opportunities and challenges in cancer. J Hematol Oncol. 12:342019. View Article : Google Scholar : PubMed/NCBI

Jiang X, Stockwell BR and Conrad M: Ferroptosis: Mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 22:266–282. 2021. View Article : Google Scholar : PubMed/NCBI

Stockwell BR: Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications. Cell. 185:2401–2421. 2022. View Article : Google Scholar : PubMed/NCBI

Peng F, Liao M, Qin R, Zhu S, Peng C, Fu L, Chen Y and Han B: Regulated cell death (RCD) in cancer: Key pathways and targeted therapies. Signal Transduct Target Ther. 7:2862022. View Article : Google Scholar : PubMed/NCBI

Diao J, Jia Y, Dai E, Liu J, Kang R, Tang D, Han L, Zhong Y and Meng L: Ferroptotic therapy in cancer: Benefits, side effects, and risks. Mol Cancer. 23:892024. View Article : Google Scholar : PubMed/NCBI

Brown AR, Hirschhorn T and Stockwell BR: Ferroptosis-disease perils and therapeutic promise. Science. 386:848–849. 2024. View Article : Google Scholar : PubMed/NCBI

Li FJ, Long HZ, Zhou ZW, Luo HY, Xu SG and Gao LC: System Xc-/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy. Front Pharmacol. 13:9102922022. View Article : Google Scholar

Ursini F and Maiorino M: Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radic Biol Med. 152:175–185. 2020. View Article : Google Scholar : PubMed/NCBI

Zhu WW, Liu Y, Yu Z and Wang HQ: SLC7A11-mediated cell death mechanism in cancer: A comparative study of disulfidptosis and ferroptosis. Front Cell Dev Biol. 13:15594232025. View Article : Google Scholar : PubMed/NCBI

Zheng J and Conrad M: Ferroptosis: When metabolism meets cell death. Physiol Rev. 105:651–706. 2025. View Article : Google Scholar

Tang D, Chen X, Kang R and Kroemer G: Ferroptosis: Molecular mechanisms and health implications. Cell Res. 31:107–125. 2021. View Article : Google Scholar

Teng Y, Gao L, Mäkitie AA, Florek E, Czarnywojtek A, Saba NF and Ferlito A: Iron, Ferroptosis, and head and neck cancer. Int J Mol Sci. 24:151272023. View Article : Google Scholar :

Yang M, Guo R, Chen X, Song G and Zhang F: Advances in the study of regulators of ferroptosis in head and neck squamous cell carcinoma (review). Int J Mol Med. 51:452023. View Article : Google Scholar :

Song A, Wu L, Zhang BX, Yang QC, Liu YT, Li H, Mao L, Xiong D, Yu HJ and Sun ZJ: Glutamine inhibition combined with CD47 blockade enhances radiotherapy-induced ferroptosis in head and neck squamous cell carcinoma. Cancer Lett. 588:2167272024. View Article : Google Scholar : PubMed/NCBI

Allevato MM, Trinh S, Koshizuka K, Nachmanson D, Nguyen TC, Yokoyama Y, Wu X, Andres A, Wang Z, Watrous J, et al: A genome-wide CRISPR screen reveals that antagonism of glutamine metabolism sensitizes head and neck squamous cell carcinoma to ferroptotic cell death. Cancer Lett. 598:2170892024. View Article : Google Scholar : PubMed/NCBI

Noh JK, Lee MK, Lee Y, Bae M, Min S, Kong M, Lee JW, Kim SI, Lee YC, Ko SG, et al: Targeting ferroptosis for improved radiotherapy outcomes in HPV-negative head and neck squamous cell carcinoma. Mol Oncol. 19:540–557. 2025. View Article : Google Scholar

Li M, Jin S, Zhang Z, Ma H and Yang X: Interleukin-6 facilitates tumor progression by inducing ferroptosis resistance in head and neck squamous cell carcinoma. Cancer Lett. 527:28–40. 2022. View Article : Google Scholar

Yang J and Gu Z: Ferroptosis in head and neck squamous cell carcinoma: From pathogenesis to treatment. Front Pharmacol. 15:12834652024. View Article : Google Scholar : PubMed/NCBI

Yuan J and Ofengeim D: A guide to cell death pathways. Nat Rev Mol Cell Biol. 25:379–395. 2024. View Article : Google Scholar

Tang D and Kroemer G: Peroxisome: The new player in ferroptosis. Signal Transduct Target Ther. 5:2732020. View Article : Google Scholar : PubMed/NCBI

Wang H, Fleishman JS, Cheng S, Wang W, Wu F and Wang Y and Wang Y: Epigenetic modification of ferroptosis by non-coding RNAs in cancer drug resistance. Mol Cancer. 23:1772024. View Article : Google Scholar : PubMed/NCBI

Dixon SJ and Olzmann JA: The cell biology of ferroptosis. Nat Rev Mol Cell Biol. 25:424–442. 2024. View Article : Google Scholar : PubMed/NCBI

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI

Sun S, Shen J, Jiang J, Wang F and Min J: Targeting ferroptosis opens new avenues for the development of novel therapeutics. Signal Transduct Target Ther. 8:3722023. View Article : Google Scholar : PubMed/NCBI

Jiang X, Peng Q, Peng M, Oyang L, Wang H, Liu Q, Xu X, Wu N, Tan S, Yang W, et al: Cellular metabolism: A key player in cancer ferroptosis. Cancer Commun (Lond). 44:185–204. 2024. View Article : Google Scholar : PubMed/NCBI

Tong X, Tang R, Xiao M, Xu J, Wang W, Zhang B, Liu J, Yu X and Shi S: Targeting cell death pathways for cancer therapy: Recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research. J Hematol Oncol. 15:1742022. View Article : Google Scholar : PubMed/NCBI

Chen X, Kang R, Kroemer G and Tang D: Organelle-specific regulation of ferroptosis. Cell Death Differ. 28:2843–2856. 2021. View Article : Google Scholar :

Chen F, Kang R, Tang D and Liu J: Ferroptosis: Principles and significance in health and disease. J Hematol Oncol. 17:412024. View Article : Google Scholar :

Dogan SA, Giacchin G, Zito E and Viscomi C: Redox signaling and stress in inherited myopathies. Antioxid Redox Signal. 37:301–323. 2022. View Article : Google Scholar : PubMed/NCBI

Wang Y, Zhang R, Wang A, Wang X, Wang X, Zhang J, Liu G, Huang K, Liu B, Hu Y, et al: COPB1 deficiency triggers osteoporosis with elevated iron stores by inducing osteoblast ferroptosis. J Orthop Translat. 51:312–328. 2025. View Article : Google Scholar : PubMed/NCBI

Chen J, Liu D, Lei L, Liu T, Pan S, Wang H, Liu Y, Qiao Y, Liu Z and Feng Q: CNPY2 aggravates renal tubular cell ferroptosis in diabetic nephropathy by regulating PERK/ATF4/CHAC1 pathway and MAM integrity. Adv Sci (Weinh). 12:e24164412025. View Article : Google Scholar : PubMed/NCBI

Loopmans S, Rohlenova K, van Brussel T, Stockmans I, Moermans K, Peredo N, Carmeliet P, Lambrechts D, Stegen S and Carmeliet G: The pentose phosphate pathway controls oxidative protein folding and prevents ferroptosis in chondrocytes. Nat Metab. 7:182–195. 2025. View Article : Google Scholar : PubMed/NCBI

Deng X, Liu T, Zhu Y, Chen J, Song Z, Shi Z and Chen H: Ca & Mn dual-ion hybrid nanostimulator boosting anti-tumor immunity via ferroptosis and innate immunity awakening. Bioact Mater. 33:483–496. 2024.

Li Q and Gan B: Uncovering the IL-1β-PCAF-NNT axis: A new player in ferroptosis and tumor immune evasion. Cancer Commun (Lond). 43:1048–1050. 2023. View Article : Google Scholar : PubMed/NCBI

Lee J and Roh JL: Ferroptosis induction via targeting metabolic alterations in head and neck cancer. Crit Rev Oncol Hematol. 181:1038872023. View Article : Google Scholar

Liu Y, Lu S, Wu LL, Yang L, Yang L and Wang J: The diversified role of mitochondria in ferroptosis in cancer. Cell Death Dis. 14:5192023. View Article : Google Scholar : PubMed/NCBI

Meng X, Peng X, Ouyang W, Li H, Na R, Zhou W, You X, Li Y, Pu X, Zhang K, et al: Musashi-2 deficiency triggers colorectal cancer ferroptosis by downregulating the MAPK signaling cascade to inhibit HSPB1 phosphorylation. Biol Proced Online. 25:322023. View Article : Google Scholar : PubMed/NCBI

Seo I, Kim SW, Hyun J, Kim YJ, Park HS, Yoon JK and Bhang SH: Enhancing viability and angiogenic efficacy of mesenchymal stem cells via HSP90α and HSP27 regulation based on ROS stimulation for wound healing. Bioeng Transl Med. 8:e105602023. View Article : Google Scholar

Liu B, Chen Z, Li Z, Zhao X, Zhang W, Zhang A, Wen L, Wang X, Zhou S and Qian D: Hsp90α promotes chemoresistance in pancreatic cancer by regulating Keap1-Nrf2 axis and inhibiting ferroptosis. Acta Biochim Biophys Sin (Shanghai). 57:295–309. 2024. View Article : Google Scholar

Ao Q, Hu H and Huang Y: Ferroptosis and endoplasmic reticulum stress in rheumatoid arthritis. Front Immunol. 15:14388032024. View Article : Google Scholar :

Long H, Zhu W, Wei L and Zhao J: Iron homeostasis imbalance and ferroptosis in brain diseases. MedComm (2020). 4:e2982023. View Article : Google Scholar : PubMed/NCBI

Feng F, He S, Li X, He J and Luo L: Mitochondria-mediated ferroptosis in diseases therapy: From molecular mechanisms to implications. Aging Dis. 15:714–738. 2024. View Article : Google Scholar :

Harrington JS, Ryter SW, Plataki M, Price DR and Choi AMK: Mitochondria in health, disease, and aging. Physiol Rev. 103:2349–2422. 2023. View Article : Google Scholar : PubMed/NCBI

Li J, Jia YC, Ding YX, Bai J, Cao F and Li F: The crosstalk between ferroptosis and mitochondrial dynamic regulatory networks. Int J Biol Sci. 19:2756–2771. 2023. View Article : Google Scholar : PubMed/NCBI

Liao P, Wang W, Wang W, Kryczek I, Li X, Bian Y, Sell A, Wei S, Grove S, Johnson JK, et al: CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell. 40:365–378.e366. 2022. View Article : Google Scholar :

Bock FJ and Tait SWG: Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. 21:85–100. 2020. View Article : Google Scholar

Ahola S and Langer T: Ferroptosis in mitochondrial cardiomyopathy. Trends Cell Biol. 34:150–160. 2024. View Article : Google Scholar

Lyamzaev KG, Panteleeva AA, Simonyan RA, Avetisyan AV and Chernyak BV: mitochondrial lipid peroxidation is responsible for ferroptosis. Cells. 12:6112023. View Article : Google Scholar :

Jelinek A, Heyder L, Daude M, Plessner M, Krippner S, Grosse R, Diederich WE and Culmsee C: Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis. Free Radic Biol Med. 117:45–57. 2018. View Article : Google Scholar : PubMed/NCBI

Wang Z, Tang S, Cai L, Wang Q, Pan D, Dong Y, Zhou H, Li J, Ji N, Zeng X, et al: DRP1 inhibition-mediated mitochondrial elongation abolishes cancer stemness, enhances glutaminolysis, and drives ferroptosis in oral squamous cell carcinoma. Br J Cancer. 130:1744–1757. 2024. View Article : Google Scholar :

Saimoto Y, Kusakabe D, Morimoto K, Matsuoka Y, Kozakura E, Kato N, Tsunematsu K, Umeno T, Kiyotani T, Matsumoto S, et al: Lysosomal lipid peroxidation contributes to ferroptosis induction via lysosomal membrane permeabilization. Nat Commun. 16:35542025. View Article : Google Scholar : PubMed/NCBI

Zhang Y, Li M, Guo Y, Liu S and Tao Y: The organelle-specific regulations and epigenetic regulators in ferroptosis. Front Pharmacol. 13:9055012022. View Article : Google Scholar : PubMed/NCBI

Qiu B, Zandkarimi F, Bezjian CT, Reznik E, Soni RK, Gu W, Jiang X and Stockwell BR: Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis. Cell. 187:1177–1190.e18. 2024. View Article : Google Scholar :

Zhao L, Zhou X, Xie F and Zhang L, Yan H, Huang J, Zhang C, Zhou F, Chen J and Zhang L: Ferroptosis in cancer and cancer immunotherapy. Cancer Commun (Lond). 42:88–116. 2022. View Article : Google Scholar :

Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A, et al: ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 13:91–98. 2017. View Article : Google Scholar :

Tang R, Xu J, Zhang B, Liu J, Liang C, Hua J, Meng Q, Yu X and Shi S: Ferroptosis, necroptosis, and pyroptosis in anticancer immunity. J Hematol Oncol. 13:1102020. View Article : Google Scholar : PubMed/NCBI

Gan B: ACSL4, PUFA, and ferroptosis: New arsenal in anti-tumor immunity. Signal Transduct Target Ther. 7:1282022. View Article : Google Scholar :

Xu X, Xu XD, Ma MQ, Liang Y, Cai YB, Zhu ZX, Xu T, Zhu L and Ren K: The mechanisms of ferroptosis and its role in atherosclerosis. Biomed Pharmacother. 171:1161122024. View Article : Google Scholar

Dai E, Chen X, Linkermann A, Jiang X, Kang R, Kagan VE, Bayir H, Yang WS, Garcia-Saez AJ, Ioannou MS, et al: A guideline on the molecular ecosystem regulating ferroptosis. Nat Cell Biol. 26:1447–1457. 2024. View Article : Google Scholar : PubMed/NCBI

Quan J, Bode AM and Luo X: ACSL family: The regulatory mechanisms and therapeutic implications in cancer. Eur J Pharmacol. 909:1743972021. View Article : Google Scholar : PubMed/NCBI

Deng W, Zhao J, Wang X, Li D, Wang M, Zheng X, Wang R, Guo Q, Zhao P, Yan H, Shen L, et al: Role of ferroptosis mediated by abnormal membrane structure in DEHP-induced reproductive injury. Free Radic Biol Med. 235:150–161. 2025. View Article : Google Scholar : PubMed/NCBI

Shahtout JL, Eshima H, Ferrara PJ, Maschek JA, Cox JE, Drummond MJ and Funai K: Inhibition of the skeletal muscle Lands cycle ameliorates weakness induced by physical inactivity. J Cachexia Sarcopenia Muscle. 15:319–330. 2024. View Article : Google Scholar :

Crielaard BJ, Lammers T and Rivella S: Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov. 16:400–423. 2017. View Article : Google Scholar :

Ru Q, Li Y, Chen L, Wu Y, Min J and Wang F: Iron homeostasis and ferroptosis in human diseases: Mechanisms and therapeutic prospects. Signal Transduct Target Ther. 9:2712024. View Article : Google Scholar : PubMed/NCBI

Yuan C, Ma Z, Xie J, Li W, Su L, Zhang G, Xu J, Wu Y, Zhang M and Liu W: The role of cell death in SARS-CoV-2 infection. Signal Transduct Target Ther. 8:3572023. View Article : Google Scholar : PubMed/NCBI

Yin J, Zhan J, Hu Q, Huang S and Lin W: Fluorescent probes for ferroptosis bioimaging: Advances, challenges, and prospects. Chem Soc Rev. 52:2011–2030. 2023. View Article : Google Scholar : PubMed/NCBI

Lee J and Roh JL: Lipid metabolism in ferroptosis: Unraveling key mechanisms and therapeutic potential in cancer. Biochim Biophys Acta Rev Cancer. 1880:1892582025. View Article : Google Scholar : PubMed/NCBI

Liu Y, Wan Y, Jiang Y, Zhang L and Cheng W: GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment. Biochim Biophys Acta Rev Cancer. 1878:1888902023. View Article : Google Scholar

Yan HF, Zou T, Tuo QZ, Xu S, Li H, Belaidi AA and Lei P: Ferroptosis: Mechanisms and links with diseases. Signal Transduct Target Ther. 6:492021. View Article : Google Scholar : PubMed/NCBI

Alvarez SW, Sviderskiy VO, Terzi EM, Papagiannakopoulos T, Moreira AL, Adams S, Sabatini DM, Birsoy K and Possemato R: NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature. 551:639–643. 2017. View Article : Google Scholar

Zhao P, Yin S, Qiu Y, Sun C and Yu H: Ferroptosis and pyroptosis are connected through autophagy: A new perspective of overcoming drug resistance. Mol Cancer. 24:232025. View Article : Google Scholar : PubMed/NCBI

Yang Y, Jiang B, Shi L, Wang L, Yang Y, Li Y, Zhang Y, Zhu Z, Zhang X and Liu X: The potential of natural herbal plants in the treatment and prevention of non-small cell lung cancer: An encounter between ferroptosis and mitophagy. J Ethnopharmacol. 346:1195552025. View Article : Google Scholar

Zhang X, Hu Y, Wang B and Yang S: Ferroptosis: Iron-mediated cell death linked to disease pathogenesis. J Biomed Res. 38:413–435. 2024. View Article : Google Scholar : PubMed/NCBI

Yao X, Zhang Y, Hao J, Duan HQ, Zhao CX, Sun C, Li B, Fan BY, Wang X, Li WX, et al: Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis. Neural Regen Res. 14:532–541. 2019. View Article : Google Scholar :

Bi G, Liang J, Bian Y, Shan G, Huang Y, Lu T, Zhang H, Jin X, Chen Z, Zhao M, et al: Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. Nat Commun. 15:24612024. View Article : Google Scholar : PubMed/NCBI

Xiao Y, Xu Z, Cheng Y, Huang R, Xie Y, Tsai HI, Zha H, Xi L, Wang K, Cheng X, et al: Fe3⁺-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma. Biomater Res. 27:632023. View Article : Google Scholar

Yong Y, Yan L, Wei J, Feng C, Yu L, Wu J, Guo M, Fan D, Yu C, Qin D, et al: A novel ferroptosis inhibitor, Thonningianin A, improves Alzheimer's disease by activating GPX4. Theranostics. 14:6161–6184. 2024. View Article : Google Scholar : PubMed/NCBI

Xia J, Si H, Yao W, Li C, Yang G, Tian Y and Hao C: Research progress on the mechanism of ferroptosis and its clinical application. Exp Cell Res. 409:1129322021. View Article : Google Scholar : PubMed/NCBI

Liu Z, Zhang H, Hong G, Bi X, Hu J, Zhang T, An Y, Guo N, Dong F, Xiao Y, et al: Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice. Mol Ther. 32:1387–1406. 2024. View Article : Google Scholar : PubMed/NCBI

Liu D, Cheng X, Wu H, Song H, Bu Y, Wang J, Zhang X, Yan C and Han Y: CREG1 attenuates doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis of cardiomyocytes. Redox Biol. 75:1032932024. View Article : Google Scholar : PubMed/NCBI

Wang D, Li X, Jiao D, Cai Y, Qian L, Shen Y, Lu Y, Zhou Y, Fu B, Sun R, et al: LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia. J Hematol Oncol. 16:302023. View Article : Google Scholar : PubMed/NCBI

Luo Z, Zheng Q, Ye S, Li Y, Chen J, Fan C, Chen J, Lei Y, Liao Q and Xi Y: HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells. Cell Death Dis. 15:2202024. View Article : Google Scholar : PubMed/NCBI

Wu F, Song C, Yin H, Chen R, Huang G, Zhang J, Chen H, Lin L, Yin J, Xie L and Liu W: Metal phenolic networks-driven bufalin homodimeric prodrug nano-coassemblies for ferroptosis-augmented tumor therapy. J Control Release. 383:1138142025. View Article : Google Scholar : PubMed/NCBI

Qiu Y, Mo C, Xu S, Chen L, Ye W, Kang Y, Chen G and Zhu T: Research progress on perioperative blood-brain barrier damage and its potential mechanism. Front Cell Dev Biol. 11:11740432023. View Article : Google Scholar : PubMed/NCBI

Hassannia B, Vandenabeele P and Vanden Berghe T: Targeting ferroptosis to iron out cancer. Cancer Cell. 35:830–849. 2019. View Article : Google Scholar : PubMed/NCBI

Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, et al: Regulation of ferroptotic cancer cell death by GPX4. Cell. 156:317–331. 2014. View Article : Google Scholar : PubMed/NCBI

Woo JH, Shimoni Y, Yang WS, Subramaniam P, Iyer A, Nicoletti P, Rodríguez Martínez M, López G, Mattioli M, Realubit R, et al: Elucidating compound mechanism of action by network perturbation analysis. Cell. 162:441–451. 2015. View Article : Google Scholar : PubMed/NCBI

Tuo QZ, Masaldan S, Southon A, Mawal C, Ayton S, Bush AI, Lei P and Belaidi AA: Characterization of selenium compounds for Anti-ferroptotic activity in neuronal cells and after cerebral ischemia-reperfusion injury. Neurotherapeutics. 18:2682–2691. 2021. View Article : Google Scholar : PubMed/NCBI

Cheu JW, Lee D, Li Q, Goh CC, Bao MH, Yuen VW, Zhang MS, Yang C, Chan CY, Tse AP, et al: Ferroptosis Suppressor Protein 1 inhibition promotes tumor ferroptosis and anti-tumor immune responses in liver cancer. Cell Mol Gastroenterol Hepatol. 16:133–159. 2023. View Article : Google Scholar : PubMed/NCBI

Mao C, Liu X, Zhang Y, Lei G, Yan Y, Lee H, Koppula P, Wu S, Zhuang L, Fang B, et al: DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature. 593:586–590. 2021. View Article : Google Scholar : PubMed/NCBI

Hai Y, Fan R, Zhao T, Lin R, Zhuang J, Deng A, Meng S, Hou Z and Wei G: A novel mitochondria-targeting DHODH inhibitor induces robust ferroptosis and alleviates immune suppression. Pharmacol Res. 202:1071152024. View Article : Google Scholar : PubMed/NCBI

Cederfjäll E, Sahin G, Kirik D and Björklund T: Design of a single AAV vector for coexpression of TH and GCH1 to establish continuous DOPA synthesis in a rat model of Parkinson's disease. Mol Ther. 20:1315–1326. 2012. View Article : Google Scholar : PubMed/NCBI

Carnicer R, Duglan D, Ziberna K, Recalde A, Reilly S, Simon JN, Mafrici S, Arya R, Roselló-Lletí E, Chuaiphichai S, et al: BH4 increases nNOS activity and preserves left ventricular function in diabetes. Circ Res. 128:585–601. 2021. View Article : Google Scholar : PubMed/NCBI

Liang D, Feng Y, Zandkarimi F, Wang H, Zhang Z, Kim J, Cai Y, Gu W, Stockwell BR and Jiang X: Ferroptosis surveillance independent of GPX4 and differentially regulated by sex hormones. Cell. 186:2748–2764.e22. 2023. View Article : Google Scholar : PubMed/NCBI

Liang C, Zhang X, Yang M and Dong X: Recent progress in ferroptosis inducers for cancer therapy. Adv Mater. 31:e19041972019. View Article : Google Scholar : PubMed/NCBI

Wang L, Liu Y, Du T, Yang H, Lei L, Guo M, Ding HF, Zhang J, Wang H, Chen X and Yan C: ATF3 promotes erastin-induced ferroptosis by suppressing system Xc. Cell Death Differ. 27:662–675. 2020. View Article : Google Scholar

Fennell D: Cancer-cell death ironed out. Nature. 572:314–315. 2019. View Article : Google Scholar : PubMed/NCBI

Mishima E and Conrad M: Nonmetabolic role for CKB in ferroptosis. Nat Cell Biol. 25:633–634. 2023. View Article : Google Scholar : PubMed/NCBI

Stockwell BR, Jiang X and Gu W: Emerging mechanisms and disease relevance of ferroptosis. Trends Cell Biol. 30:478–490. 2020. View Article : Google Scholar : PubMed/NCBI

Nakamura T, Hipp C, Santos Dias Mourão A, Borggräfe J, Aldrovandi M, Henkelmann B, Wanninger J, Mishima E, Lytton E, Emler D, et al: Phase separation of FSP1 promotes ferroptosis. Nature. 619:371–377. 2023. View Article : Google Scholar : PubMed/NCBI

Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, et al: The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 575:688–692. 2019. View Article : Google Scholar : PubMed/NCBI

Wang Y, Lilienfeldt N and Hekimi S: Understanding coenzyme Q. Physiol Rev. 104:1533–1610. 2024. View Article : Google Scholar : PubMed/NCBI

Mishima E, Nakamura T, Zheng J, Zhang W, Mourão ASD, Sennhenn P and Conrad M: DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition. Nature. 619:E9–E18. 2023. View Article : Google Scholar : PubMed/NCBI

Liang D, Deng L and Jiang X: A new checkpoint against ferroptosis. Cell Res. 30:3–4. 2020. View Article : Google Scholar :

Garcia-Bermudez J and Birsoy K: A mitochondrial gatekeeper that helps cells escape death by ferroptosis. Nature. 593:514–515. 2021. View Article : Google Scholar : PubMed/NCBI

Vasan K, Werner M and Chandel NS: Mitochondrial metabolism as a target for cancer therapy. Cell Metab. 32:341–352. 2020. View Article : Google Scholar : PubMed/NCBI

Mao C, Lei G, Zhuang L and Gan B: Phospholipase iPLA2β acts as a guardian against ferroptosis. Cancer Commun (Lond). 41:1082–1085. 2021. View Article : Google Scholar : PubMed/NCBI

Xiang H, Lyu Q, Chen S, Ouyang J, Xiao D, Liu Q, Long H, Zheng X, Yang X and Lu H: PACS2/CPT1A/DHODH signaling promotes cardiomyocyte ferroptosis in diabetic cardiomyopathy. Cardiovasc Diabetol. 23:4322024. View Article : Google Scholar : PubMed/NCBI

Wu MF, Peng X, Zhang MC, Guo H and Xie HT: Ferroptosis and PANoptosis under hypoxia pivoting on the crosstalk between DHODH and GPX4 in corneal epithelium. Free Radic Biol Med. 228:173–182. 2025. View Article : Google Scholar : PubMed/NCBI

Zhang L, Rao F, Zhang K, Khandrika S, Das M, Vaingankar SM, Bao X, Rana BK, Smith DW, Wessel J, et al: Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing nitric oxide, autonomic activity, and cardiovascular risk. J Clin Invest. 117:2658–2671. 2007. View Article : Google Scholar : PubMed/NCBI

Jiang Y, Zhao J, Li R, Liu Y, Zhou L, Wang C, Lv C, Gao L and Cui D: CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis. J Exp Clin Cancer Res. 41:3072022. View Article : Google Scholar : PubMed/NCBI

Nishizawa H, Yamanaka M and Igarashi K: Ferroptosis: Regulation by competition between NRF2 and BACH1 and propagation of the death signal. FEBS J. 290:1688–1704. 2023. View Article : Google Scholar

Kraft VAN, Bezjian CT, Pfeiffer S, Ringelstetter L, Müller C, Zandkarimi F, Merl-Pham J, Bao X, Anastasov N, Kössl J, et al: GTP Cyclohydrolase 1/Tetrahydrobiopterin counteract ferroptosis through lipid remodeling. ACS Cent Sci. 6:41–53. 2020. View Article : Google Scholar : PubMed/NCBI

Pope LE and Dixon SJ: Regulation of ferroptosis by lipid metabolism. Trends Cell Biol. 33:1077–1087. 2023. View Article : Google Scholar : PubMed/NCBI

Papsdorf K, Miklas JW, Hosseini A, Cabruja M, Morrow CS, Savini M, Yu Y, Silva-García CG, Haseley NR, Murphy LM, et al: Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids. Nat Cell Biol. 25:672–684. 2023. View Article : Google Scholar : PubMed/NCBI

Mori H, Peterson SK, Simmermon RC, Overmyer KA, Nishii A, Paulsson E, Li Z, Jen A, Uranga RM, Maung JN, et al: Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes. Mol Metab. 83:1019162024. View Article : Google Scholar : PubMed/NCBI

Zhang XD, Liu ZY, Wang MS, Guo YX, Wang XK, Luo K, Huang S and Li RF: Mechanisms and regulations of ferroptosis. Front Immunol. 14:12694512023. View Article : Google Scholar : PubMed/NCBI

Li S, Zhang G, Hu J, Tian Y and Fu X: Ferroptosis at the nexus of metabolism and metabolic diseases. Theranostics. 14:5826–5852. 2024. View Article : Google Scholar : PubMed/NCBI

Rodencal J, Kim N, He A, Li VL, Lange M, He J, Tarangelo A, Schafer ZT, Olzmann JA, Long JZ, et al: Sensitization of cancer cells to ferroptosis coincident with cell cycle arrest. Cell Chem Biol. 31:234–248.e13. 2024. View Article : Google Scholar :

Arnér ESJ and Schmidt EE: Unresolved questions regarding cellular cysteine sources and their possible relationships to ferroptosis. Adv Cancer Res. 162:1–44. 2024. View Article : Google Scholar : PubMed/NCBI

Zhou Q, Meng Y, Le J, Sun Y, Dian Y, Yao L, Xiong Y, Zeng F, Chen X and Deng G: Ferroptosis: Mechanisms and therapeutic targets. MedComm (2020). 5:e700102024. View Article : Google Scholar : PubMed/NCBI

Bhat KP, Vijay J, Vilas CK, Asundi J, Zou J, Lau T, Cai X, Ahmed M, Kabza M, Weng J, et al: CRISPR activation screens identify the SWI/SNF ATPases as suppressors of ferroptosis. Cell Rep. 43:1143452024. View Article : Google Scholar : PubMed/NCBI

Riegman M, Sagie L, Galed C, Levin T, Steinberg N, Dixon SJ, Wiesner U, Bradbury MS, Niethammer P, Zaritsky A and Overholtzer M: Ferroptosis occurs through an osmotic mechanism and propagates independently of cell rupture. Nat Cell Biol. 22:1042–1048. 2020. View Article : Google Scholar : PubMed/NCBI

Pedrera L, Espiritu RA, Ros U, Weber J, Schmitt A, Stroh J, Hailfinger S, von Karstedt S and García-Sáez AJ: Ferroptotic pores induce Ca2⁺ fluxes and ESCRT-III activation to modulate cell death kinetics. Cell Death Differ. 28:1644–1657. 2021. View Article : Google Scholar

Veglia Tranchese R, Battista S, Cerchia L and Fedele M: Ferroptosis in cancer: Epigenetic control and therapeutic opportunities. Biomolecules. 14:14432024. View Article : Google Scholar : PubMed/NCBI

Han Y, Gao X, Wu N, Jin Y, Zhou H, Wang W, Liu H, Chu Y, Cao J, Jiang M, et al: Long noncoding RNA LINC00239 inhibits ferroptosis in colorectal cancer by binding to Keap1 to stabilize Nrf2. Cell Death Dis. 13:7422022. View Article : Google Scholar : PubMed/NCBI

Tao Q and Li Y, Zhang W, Zhang M, Li X, Jin H, Zheng J and Li Y: Long non-coding RNA ZFAS1 promotes ferroptosis by regulating the miR-185-5p/SLC25A28 axis in clear cell renal cell carcinoma. Int J Biol Macromol. 304:1406022025. View Article : Google Scholar : PubMed/NCBI

Liu Y, Li L, Yang Z, Wen D and Hu Z: Circular RNA circACAP2 suppresses ferroptosis of cervical cancer during malignant progression by miR-193a-5p/GPX4. J Oncol. 2022:52288742022.PubMed/NCBI

Chen SJ, Zhang J, Zhou T, Rao SS, Li Q, Xiao LY, Wei ST and Zhang HF: Epigenetically upregulated NSUN2 confers ferroptosis resistance in endometrial cancer via m⁵C modification of SLC7A11 mRNA. Redox Biol. 69:1029752024. View Article : Google Scholar

Sultana A and Rana S: Mechanisms underlying obesity-malignancy connection: A systematic narrative review. J Physiol Biochem. 81:403–439. 2025. View Article : Google Scholar : PubMed/NCBI

Zhang X, Tang B, Luo J, Yang Y, Weng Q, Fang S, Zhao Z, Tu J, Chen M and Ji J: Cuproptosis, ferroptosis and PANoptosis in tumor immune microenvironment remodeling and immunotherapy: Culprits or new hope. Mol Cancer. 23:2552024. View Article : Google Scholar : PubMed/NCBI

He F, Chen Z, Deng W, Zhan T, Huang X, Zheng Y and Yang H: Development and validation of a novel ferroptosis-related gene signature for predicting prognosis and immune microenvironment in head and neck squamous cell carcinoma. Int Immunopharmacol. 98:1077892021. View Article : Google Scholar : PubMed/NCBI

Qi YL, Wang HR, Chen LL, Duan YT, Yang SY and Zhu HL: Recent advances in small-molecule fluorescent probes for studying ferroptosis. Chem Soc Rev. 51:7752–7778. 2022. View Article : Google Scholar : PubMed/NCBI

Shi JX, Zhang ZC, Yin HZ, Piao XJ, Liu CH, Liu QJ, Zhang JC, Zhou WX, Liu FC, Yang F, et al: RNA m6A modification in ferroptosis: Implications for advancing tumor immunotherapy. Mol Cancer. 23:2132024. View Article : Google Scholar : PubMed/NCBI

Ma L, Chen C, Zhao C, Li T, Ma L, Jiang J, Duan Z, Si Q, Chuang TH, Xiang R and Luo Y: Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer. Signal Transduct Target Ther. 9:642024. View Article : Google Scholar : PubMed/NCBI

Bao X, Luo X, Bai X, Lv Y, Weng X, Zhang S, Leng Y, Huang J, Dai X, Wang Y, et al: Cigarette tar mediates macrophage ferroptosis in atherosclerosis through the hepcidin/FPN/SLC7A11 signaling pathway. Free Radic Biol Med. 201:76–88. 2023. View Article : Google Scholar : PubMed/NCBI

Dai C, Kong B, Qin T, Xiao Z, Fang J, Gong Y, Zhu J, Liu Q, Fu H, Meng H, et al: Inhibition of ferroptosis reduces susceptibility to frequent excessive alcohol consumption-induced atrial fibrillation. Toxicology. 465:1530552022. View Article : Google Scholar

Lenoci D, Serafini MS, Lucchetta M, Cavalieri S, Brakenhoff RH, Hoebers F, Scheckenbach K, Poli T, Licitra L and De Cecco L: Ferroptosis-related gene signatures: Prognostic role in HPV-positive oropharyngeal squamous cell carcinoma. Cancers (Basel). 17:5302025. View Article : Google Scholar : PubMed/NCBI

Hémon A, Louandre C, Lailler C, Godin C, Bottelin M, Morel V, François C, Galmiche A and Saidak Z: SLC7A11 as a biomarker and therapeutic target in HPV-positive head and neck squamous cell carcinoma. Biochem Biophys Res Commun. 533:1083–1087. 2020. View Article : Google Scholar : PubMed/NCBI

Zhou P, Peng X, Zhang K, Cheng J, Tang M, Shen L, Zhou Q, Li D and Yang L: HAT1/HDAC2 mediated ACSL4 acetylation confers radiosensitivity by inducing ferroptosis in nasopharyngeal carcinoma. Cell Death Dis. 16:1602025. View Article : Google Scholar : PubMed/NCBI

Lee J, Seo Y and Roh JL: Emerging therapeutic strategies targeting GPX4-Mediated ferroptosis in head and neck cancer. Int J Mol Sci. 26:64522025. View Article : Google Scholar : PubMed/NCBI

Liao Q, Yang J, Lu Z, Jiang Q, Gong Y, Liu L, Peng H, Wang Q, Zhang X and Liu Z: FTH1 indicates poor prognosis and promotes metastasis in head and neck squamous cell carcinoma. PeerJ. 11:e164932023. View Article : Google Scholar : PubMed/NCBI

Zhang Z, Zhu H, Zhao C, Liu D, Luo J, Ying Y and Zhong Y: DDIT4 promotes malignancy of head and neck squamous cell carcinoma. Mol Carcinog. 62:332–347. 2023. View Article : Google Scholar

Roh JL: Targeting ferroptosis suppressor protein 1 in cancer therapy: Implications and perspectives, with emphasis on head and neck cancer. Crit Rev Oncol Hematol. 202:1044402024. View Article : Google Scholar : PubMed/NCBI

Lee J and Roh JL: Altered iron metabolism as a target for ferroptosis induction in head and neck cancer. Cell Oncol (Dordr). 46:801–810. 2023. View Article : Google Scholar : PubMed/NCBI

Lee J, You JH and Roh JL: Poly(rC)-binding protein 1 represses ferritinophagy-mediated ferroptosis in head and neck cancer. Redox Biol. 51:1022762022. View Article : Google Scholar : PubMed/NCBI

Roh JL, Kim EH, Jang H and Shin D: Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol. 11:254–262. 2017. View Article : Google Scholar :

Shin D, Kim EH, Lee J and Roh JL: Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer. Free Radic Biol Med. 129:454–462. 2018. View Article : Google Scholar : PubMed/NCBI

Zhang Y, Swanda RV, Nie L, Liu X, Wang C, Lee H, Lei G, Mao C, Koppula P, Cheng W, et al: mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation. Nat Commun. 12:15892021. View Article : Google Scholar : PubMed/NCBI

Shin D, Lee J, You JH, Kim D and Roh JL: Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer. Redox Biol. 30:1014182020. View Article : Google Scholar : PubMed/NCBI

Chung CH, Lin CY, Chen CY, Hsueh CW, Chang YW, Wang CC, Chu PY, Tai SK and Yang MH: Ferroptosis signature shapes the immune profiles to enhance the response to immune checkpoint inhibitors in head and neck cancer. Adv Sci (Weinh). 10:e22045142023. View Article : Google Scholar : PubMed/NCBI

Zhang X, Huang Z, Xie Z, Chen Y, Zheng Z, Wei X, Huang B, Shan Z, Liu J, Fan S, et al: Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via enhancing methylation of GPX4. Free Radic Biol Med. 160:552–565. 2020. View Article : Google Scholar : PubMed/NCBI

Lee J and Roh JL: Induction of ferroptosis in head and neck cancer: A novel bridgehead for fighting cancer resilience. Cancer Lett. 546:2158542022. View Article : Google Scholar : PubMed/NCBI

Lee J, You JH, Kim MS and Roh JL: Epigenetic reprogramming of epithelial-mesenchymal transition promotes ferroptosis of head and neck cancer. Redox Biol. 37:1016972020. View Article : Google Scholar : PubMed/NCBI

Cai J, Yi M, Tan Y, Li X, Li G, Zeng Z, Xiong W and Xiang B: Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ. J Exp Clin Cancer Res. 40:1902021. View Article : Google Scholar

Duan X, Chan C and Lin W: Nanoparticle-mediated immunogenic cell death enables and potentiates cancer immunotherapy. Angew Chem Int Ed Engl. 58:670–680. 2019. View Article : Google Scholar

Wang W, Green M, Choi JE, Gijón M, Kennedy PD, Johnson JK, Liao P, Lang X, Kryczek I, Sell A, et al: CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 569:270–274. 2019. View Article : Google Scholar : PubMed/NCBI

Stockwell BR and Jiang X: A physiological function for ferroptosis in tumor suppression by the immune system. Cell Metab. 30:14–15. 2019. View Article : Google Scholar : PubMed/NCBI

Zhang C, Liu X, Jin S, Chen Y and Guo R: Ferroptosis in cancer therapy: A novel approach to reversing drug resistance. Mol Cancer. 21:472022. View Article : Google Scholar : PubMed/NCBI

Yuan Z, Wang X, Qin B, Hu R, Miao R, Zhou Y, Wang L and Liu T: Targeting NQO1 induces ferroptosis and triggers anti-tumor immunity in immunotherapy-resistant KEAP1-deficient cancers. Drug Resist Updat. 77:1011602024. View Article : Google Scholar

Ma X, Xiao L, Liu L, Ye L, Su P, Bi E, Wang Q, Yang M, Qian J and Yi Q: CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability. Cell Metab. 33:1001–1012.e1005. 2021. View Article : Google Scholar

Lee J, You JH, Shin D and Roh JL: Inhibition of glutaredoxin 5 predisposes cisplatin-resistant head and neck cancer cells to ferroptosis. Theranostics. 10:7775–7786. 2020. View Article : Google Scholar : PubMed/NCBI

Demuynck R, Efimova I, Naessens F and Krysko DV: Immunogenic ferroptosis and where to find it? J Immunother Cancer. 9:e0034302021. View Article : Google Scholar : PubMed/NCBI

Wiernicki B, Maschalidi S, Pinney J, Adjemian S, Vanden Berghe T, Ravichandran KS and Vandenabeele P: Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity. Nat Commun. 13:36762022. View Article : Google Scholar : PubMed/NCBI

Zhang DD: Natural inhibitor found for cell death by ferroptosis. Nature. 626:269–270. 2024. View Article : Google Scholar : PubMed/NCBI

Hadian K and Stockwell BR: SnapShot: Ferroptosis. Cell. 181:1188–1188.e1. 2020. View Article : Google Scholar : PubMed/NCBI

Chen L, Lin W, Zhang H, Geng S, Le Z, Wan F, Huang Q, Chen H, Liu X, Lu JJ and Kong L: TRIB3 promotes malignancy of head and neck squamous cell carcinoma via inhibiting ferroptosis. Cell Death Dis. 15:1782024. View Article : Google Scholar : PubMed/NCBI

Jia X, Tian J, Fu Y, Wang Y, Yang Y, Zhang M, Yang C and Liu Y: Identification of AURKA as a biomarker associated with cuproptosis and ferroptosis in HNSCC. Int J Mol Sci. 25:43722024. View Article : Google Scholar :