Molecular mechanisms and therapeutic advances of ferroptosis in radiotherapy resistance of nasopharyngeal carcinoma

Yue Hu; Chen Zhao

doi:10.1016/j.jpha.2026.101576

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Yue Hu, Chen Zhao. Molecular mechanisms and therapeutic advances of ferroptosis in radiotherapy resistance of nasopharyngeal carcinoma[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101576

Citation:

Yue Hu, Chen Zhao. Molecular mechanisms and therapeutic advances of ferroptosis in radiotherapy resistance of nasopharyngeal carcinoma[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101576

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Molecular mechanisms and therapeutic advances of ferroptosis in radiotherapy resistance of nasopharyngeal carcinoma

doi: 10.1016/j.jpha.2026.101576

Yue Hu,
Chen Zhao^,

Department of Otolaryngology, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China

Funds:

The authors would like to acknowledge the assistance from China Medical University for this article.

Received Date: Apr. 01, 2025
Accepted Date: Feb. 02, 2026
Rev Recd Date: Feb. 01, 2026
Available Online: Feb. 04, 2026

Abstract

Abstract

Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance leads to poor outcomes. Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, is central to the radiation response in NPC. Resistant cells maintain redox balance primarily via the solute carrier family 7 member 11 (SLC7A11)/glutathione (GSH)/GSH peroxidase 4 (GPX4) axis, which detoxifies lipid peroxides; inhibiting this pathway restores ferroptotic death and radiosensitivity. The ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10) system provides a parallel antioxidant defense, while acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated incorporation of polyunsaturated fatty acids (PUFAs) promotes ferroptosis susceptibility. Dysregulated iron metabolism, through transferrin (Tf) receptor 1 (TfR1)/ divalent metal transporter 1 (DMT1)-mediated uptake and ferritinophagy, elevates the labile iron pool, fueling peroxidation. The hypoxic tumor microenvironment and the kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway further reinforce these defenses, and epstein-barr virus (EBV) infection also suppresses ferroptosis. Translationally, ferroptosis inducers synergize with radiotherapy, and nanodelivery strategies show promise. This review synthesizes these mechanisms and proposes that biomarker-guided approaches to modulate ferroptosis can overcome clinical radioresistance, offering a promising strategy to improve tumor control in NPC.
- Ferroptosis,
- Nasopharyngeal carcinoma,
- Radiotherapy resistance,
- Molecular mechanism,
- Therapeutic strategy

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References(139)

References

[1]	Y.P. Chen, A.T.C. Chan, Q.T. Le, et al., Nasopharyngeal carcinoma, Lancet. 394 (2019) 64-80.
[2]	J.Y. Li, Y.P. Chen, Y.Q. Li, et al., Chemotherapeutic and targeted agents can modulate the tumor microenvironment and increase the efficacy of immune checkpoint blockades, Mol. Cancer. 20 (2021), 27.
[3]	Z.Y. Su, P.Y. Siak, Y.Y. Lwin, et al., Epidemiology of nasopharyngeal carcinoma: current insights and future outlook, Cancer. Metastasis. Rev. 43 (2024) 919-939.
[4]	Q. Liu, H. Wang, Z. Chen, et al., Global, regional, and national epidemiology of nasopharyngeal carcinoma in middle-aged and elderly patients from 1990 to 2021, Ageing. Res. Rev. 104 (2025), 102613.
[5]	F. Dwijayanti, A. Prabawa, Besral, et al., The five-year survival rate of patients with nasopharyngeal carcinoma based on tumor response after receiving neoadjuvant chemotherapy, followed by chemoradiation, in Indonesia: A retrospective study, Oncology 98 (2020) 154-160.
[6]	F. Liu, T. Jin, L. Liu, et al., The role of concurrent chemotherapy for stage II nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A systematic review and meta-analysis, PLoS. One 13 (2018), e0194733.
[7]	H.Y. Wang, Y.L. Chang, K.F. To, et al., A new prognostic histopathologic classification of nasopharyngeal carcinoma, Chin. J. Cancer 35 (2016), 41.
[8]	X. Sun, S. Su, C. Chen, et al., Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: An analysis of survival and treatment toxicities, Radiother. Oncol. 110 (2014) 398-403.
[9]	Z. Dai, B. Lin, M. Qin, et al., METTL3-mediated m6A modification of SLC7A11 enhances nasopharyngeal carcinoma radioresistance by inhibiting ferroptosis, Int. J. Biol. Sci. 21 (2025) 1837-1851.
[10]	W.M. Huang, Z.X. Li, Y.H. Wu, et al., m6A demethylase FTO renders radioresistance of nasopharyngeal carcinoma via promoting OTUB1-mediated anti-ferroptosis, Transl. Oncol. 27 (2023), 101576.
[11]	R. You, Y.P. Liu, P.Y. Huang, et al., Efficacy and safety of locoregional radiotherapy with chemotherapy vs chemotherapy alone in de novo metastatic nasopharyngeal carcinoma: A multicenter phase 3 randomized clinical trial, JAMA Oncol. 6 (2020) 1345-1352.
[12]	H.L. Li, N.H. Deng, J.X. Xiao, et al., Cross-link between ferroptosis and nasopharyngeal carcinoma: New approach to radiotherapy sensitization, .Oncol. Lett. 22 (2021), 770.
[13]	A. Amos, N. Jiang, D. Zong, et al., Depletion of SOD2 enhances nasopharyngeal carcinoma cell radiosensitivity via ferroptosis induction modulated by DHODH inhibition, BMC Cancer 23 (2023), 117.
[14]	G. Lei, Y. Zhang, P. Koppula, et al., The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression, Cell Res. 30 (2020) 146-162.
[15]	Y. Yang, T. Zhu, X. Wang, et al., ACSL3 and ACSL4, Distinct roles in ferroptosis and cancers, Cancers (Basel) 14 (2022), 5896.
[16]	F. Yang, H. Gong, S. Chen, et al., Depletion of SLC7A11 sensitizes nasopharyngeal carcinoma cells to ionizing radiation, Protein. Pept. Lett. 31 (2024) 323-331.
[17]	S. Zhang, W. Xin, G.J. Anderson, et al., Double-edge sword roles of iron in driving energy production versus instigating ferroptosis, Cell. Death. Dis. 13 (2022), 40.
[18]	S. Chen, Y. Chen, Y. Zhang, et al., Iron metabolism and ferroptosis in epilepsy, Front. Neurosci. 14 (2020), 601193.
[19]	Q. Guo, L. Li, S. Hou, et al., The role of iron in cancer progression, Front. Oncol. 11 (2021), 778492.
[20]	J. Liu, C. Zhang, J. Wang, et al., The regulation of ferroptosis by tumor suppressor p53 and its pathway, Int. J. Mol. Sci. 21 (2020), 8387.
[21]	C. Lin, J. Zong, W. Lin, et al., EBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-kappaB and ERK1/2 pathways, J. Exp. Clin. Cancer Res. 37 (2018), 283.
[22]	L. Yuan, S. Li, Q. Chen, et al., EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma, Cell Death. Differ. 29 (2022), 1513-1527.
[23]	S.J. Dixon, K.M. Lemberg, M.R. Lamprecht, et al., Ferroptosis: An iron-dependent form of nonapoptotic cell death, Cell. 149 (2012) 1060-1072.
[24]	B.R. Stockwell, Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications, Cell 185 (2022) 2401-2421.
[25]	X. Tong, R. Tang, M. Xiao, et al., Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research, J. Hematol. Oncol. 15 (2022), 174.
[26]	J. Su, C. Bian, Z. Zheng, et al., Cooperation effects of radiation and ferroptosis on tumor suppression and radiation injury, Front. Cell. Dev. Biol. 10 (2022), 951116.
[27]	X. Yin, G. Zhu, Q. Wang, et al., Ferroptosis, a new insight into acute lung injury, Front. Pharmacol. 12 (2021), 709538.
[28]	J. Arabpour, K. Rezaei, J.Y. Khojini, et al., The potential role and mechanism of circRNAs in Ferroptosis: A comprehensive review, Pathol. Res. Pract. 255 (2024), 155203.
[29]	Y. Zhao, Z. Huang, H. Peng, Molecular mechanisms of ferroptosis and its roles in hematologic malignancies, Front. Oncol. 11 (2021), 743006.
[30]	D. Qi, M. Peng, Ferroptosis-mediated immune responses in cancer, Front. Immunol. 14 (2023), 1188365.
[31]	X. Gou, X. Tang, C. Liu, et al., Ferroptosis: A new mechanism of traditional Chinese medicine for treating hematologic malignancies, Front. Oncol. 14 (2024), 1469178.
[32]	S. He, C. Luo, F. Shi, et al., The Emerging role of ferroptosis in ebv-associated cancer: Implications for cancer therapy, Biology (Basel) 13 (2024), 543.
[33]	X. Lang, M.D. Green, W. Wang, et al., Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11, Cancer Discov. 9 (2019) 1673-1685.
[34]	S. Doll, F.P. Freitas, R. Shah, et al., FSP1 is a glutathione-independent ferroptosis suppressor, Nature 575 (2019) 693-698.
[35]	G. Lei, C. Mao, Y. Yan, et al., Ferroptosis, radiotherapy, and combination therapeutic strategies, Protei. Cell. 12 (2021) 836-857.
[36]	W. Lin, C. Wang, G. Liu, et al., SLC7A11/xCT in cancer: Biological functions and therapeutic implications, Am. J. Cancer. Res. 10 (2020) 3106-3126.
[37]	M. Shi, J. Du, J. Shi, et al., Ferroptosis-related gene ATG5 is a novel prognostic biomarker in nasopharyngeal carcinoma and head and neck squamous cell carcinoma, Front. Bioeng. Biotechnol. 10 (2022), 1006535.
[38]	H. Ni, H. Qin, C. Sun, et al., MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis, Stem. Cell Res. Ther. 12 (2021), 325.
[39]	D. Wang, L. Tang, M. Chen, et al., Nanocarriers targeting circular RNA ADARB1 boost radiosensitivity of nasopharyngeal carcinoma through synergically promoting ferroptosis, ACS. Nano. 18 (2024) 31055-31075.
[40]	S. Liu, H.L. Zhang, J. Li, et al., Tubastatin A potently inhibits GPX4 activity to potentiate cancer radiotherapy through boosting ferroptosis, Redox. Biol. 62 (2023), 102677.
[41]	D. Baiskhanova, H. Schafer, The role of Nrf2 in the regulation of mitochondrial function and ferroptosis in pancreatic cancer, Antioxidants (Basel) 13 (2024), 696.
[42]	S. Wu, C. Zhu, D. Tang, et al., The role of ferroptosis in lung cancer, Biomark Res. 9 (2021), 82.
[43]	Y.B. Zuo, Y.F. Zhang, R. Zhang, et al., Ferroptosis in cancer progression: Role of noncoding RNAs, Int. J. Biol. Sci. 18 (2022) 1829-1843.
[44]	B. Zhou, J. Liu, R. Kang, et al., Ferroptosis is a type of autophagy-dependent cell death, Semin. Cancer Biol. 66 (2020) 89-100.
[45]	M.R. Liu, W.T. Zhu, D.S. Pei, System Xc−: A key regulatory target of ferroptosis in cancer, Invest. New Drugs 39 (2021) 1123-1131.
[46]	F.J. Li, H.Z. Long, Z.W. Zhou, et al., System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy, Front. Pharmacol. 13 (2022), 910292.
[47]	Y. Wu, C. Yu, M. Luo, et al., Ferroptosis in cancer treatment: Another way to Rome, Front. Oncol. 10 (2020), 571127.
[48]	Z. Song, J. Wang, L. Zhang, Ferroptosis: A new mechanism in diabetic cardiomyopathy, Int. J. Med. Sci. 21 (2024) 612-622.
[49]	J.P. De Col, E.P. de Lima, F.M. Pompeu, et al., Underlying mechanisms behind the brain-gut-liver axis and metabolic-associated fatty liver disease (MAFLD): An update, Int. J. Mol. Sci. 25 (2024), 3694.
[50]	J. Mi, Y. Wang, S. He, et al., LncRNA HOTAIRM1 promotes radioresistance in nasopharyngeal carcinoma by modulating FTO acetylation-dependent alternative splicing of CD44, Neoplasia 56 (2024), 101034.
[51]	Y. Wu, S. Zhang, X. Gong, et al., The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression, Mol. Cancer 19 (2020), 39.
[52]	Y. Yang, Y. Lu, C. Zhang, et al., Phenazine derivatives attenuate the stemness of breast cancer cells through triggering ferroptosis, Cell. Mol. Life. Sci. 79 (2022), 360.
[53]	Y. Wang, D. Yan, J. Liu, et al., Protein modification and degradation in ferroptosis, Redox. Biol. 75 (2024), 103259.
[54]	M. Zhang, M. Guo, Y. Gao, et al., Mechanisms and therapeutic targets of ferroptosis: Implications for nanomedicine design, J. Pharm. Anal. 14 (2024), 100960.
[55]	K. Pierzynowska, E. Rintz, L. Gaffke, et al., Ferroptosis and its modulation by autophagy in light of the pathogenesis of lysosomal storage diseases, Cells 10 (2021), 365.
[56]	B. Jia, J. Li, Y. Song, et al., ACSL4-mediated ferroptosis and its potential role in central nervous system diseases and injuries, Int. J. Mol. Sci. 24 (2023), 10021.
[57]	A. Bezawork-Geleta, J. Dimou, M.J. Watt, Lipid droplets and ferroptosis as new players in brain cancer glioblastoma progression and therapeutic resistance, Front. Oncol. 12 (2022), 1085034.
[58]	D. Li, Y. Li, The interaction between ferroptosis and lipid metabolism in cancer, Signal. Transduct. Target. Ther. 5 (2020), 108.
[59]	M. Yamamoto, T.W. Kensler, H. Motohashi, The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis, Physiol. Rev. 98 (2018) 1169-1203.
[60]	X. Sun, Z. Ou, R. Chen, et al., Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells, Hepatology 63 (2016), 173-184.
[61]	Z. Fan, A.K. Wirth, D. Chen, et al., Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis, Oncogenesis 6 (2017), e371.
[62]	P. Koppula, L. Zhuang, B. Gan, Cystine transporter SLC7A11/xCT in cancer: Ferroptosis, nutrient dependency, and cancer therapy, Protein Cell. 12 (2021) 599-620.
[63]	N. Li, W. Jiang, W. Wang, et al., Ferroptosis and its emerging roles in cardiovascular diseases, Pharmacol. Res. 166 (2021), 105466.
[64]	H. Zhang, J. Pan, S. Huang, et al., Hydrogen sulfide protects cardiomyocytes from doxorubicin-induced ferroptosis through the SLC7A11/GSH/GPx4 pathway by Keap1 S-sulfhydration and Nrf2 activation, Redox. Biol. 70 (2024), 103066.
[65]	W.S. Yang, K.J. Kim, M.M. Gaschler, et al., Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis, Proc. Natl. Acad. Sci. U S A 113 (2016) E4966-E4975.
[66]	J. Yin, X. Meng, L. Peng, et al., Ferroptosis and cancer immunotherapy, Curr. Mol. Med. 23 (2023) 401-409.
[67]	C. Li, R. Liu, Z. Xiong, et al., Ferroptosis: a potential target for the treatment of atherosclerosis, Acta. Biochim. Biophys. Sin (Shanghai) 56 (2024) 331-344.
[68]	D. Coradduzza, A. Congiargiu, Z. Chen, et al., Ferroptosis and senescence: A systematic review, Int. J. Mol. Sci. 24 (2023), 3658.
[69]	H. Ma, Y. Dong, Y. Chu, et al., The mechanisms of ferroptosis and its role in alzheimer's disease, Front. Mol. Biosci. 9 (2022), 965064.
[70]	K. Miki, M. Yagi, D. Kang, et al., Glucose starvation causes ferroptosis-mediated lysosomal dysfunction, iScience. 27 (2024), 109735.
[71]	Y. Henning, U.S. Blind, S. Larafa, et al., Hypoxia aggravates ferroptosis in RPE cells by promoting the Fenton reaction, Cell. Death. Dis. 13 (2022), 662.
[72]	C. Peng, Q. Ai, F. Zhao, et al., Quercetin attenuates cerebral ischemic injury by inhibiting ferroptosis via Nrf2/HO-1 signaling pathway, Eur. J. Pharmacol. 963 (2024), 176264.
[73]	S. Gensluckner, B. Wernly, C. Datz, et al., Iron, oxidative stress, and metabolic dysfunction-associated steatotic liver disease, Antioxidants (Basel) 13 (2024), 208.
[74]	L. Deng, S. He, N. Guo, et al., Molecular mechanisms of ferroptosis and relevance to inflammation, Inflamm. Res. 72 (2023) 281-299.
[75]	X. Zheng, Y. Liang, C. Zhang, Ferroptosis regulated by hypoxia in cells, Cells. 12 (2023), 1050.
[76]	W. Cai, S. Wu, Z. Lin, et al., Hypoxia-induced BAP1 enhances erastin-induced ferroptosis in nasopharyngeal carcinoma by stabilizing H2A, Cancer Cell. Int. 24 (2024), 307.
[77]	X. Gao, W. Hu, D. Qian, et al., The mechanisms of ferroptosis under hypoxia, Cell. Mol. Neurobiol. 43 (2023) 3329-3341.
[78]	C.H. Hsieh, Y.J. Lin, W.L. Chen, et al., HIF-1alpha triggers long-lasting glutamate excitotoxicity via system Xc− in cerebral ischaemia-reperfusion, J. Pathol. 241 (2017) 337-349.
[79]	A. Elmetwalli, Ferroptosis and the cGAS-STING pathway into precision nano-immuno-theranostics: A mechanistic paradigm for reversing drug resistance in hepatocellular carcinoma, Drug Resist. Updat. 84 (2026), 101326.
[80]	M.S. Mortensen, J. Ruiz, J.L. Watts, Polyunsaturated fatty acids drive lipid peroxidation during ferroptosis, Cells 12 (2023), 804.
[81]	Y. Shan, B. You, S. Shi, et al., Hypoxia-induced matrix metalloproteinase-13 expression in exosomes from nasopharyngeal carcinoma enhances metastases, Cell Death. Dis. 9 (2018), 382.
[82]	M. Yi, J. Yang, W. Li, et al., The NOR1/OSCP1 proteins in cancer: From epigenetic silencing to functional characterization of a novel tumor suppressor, J. Cancer. 8 (2017) 626-635.
[83]	Z. Xiu, Y. Zhu, J. Han, et al., Caryophyllene oxide induces ferritinophagy by regulating the NCOA4/FTH1/LC3 pathway in hepatocellular carcinoma, Front. Pharmacol. 13 (2022), 930958.
[84]	C. Fan, Y. Tang, J. Wang, et al., The emerging role of Epstein-Barr virus encoded microRNAs in nasopharyngeal carcinoma, J. Cancer 9 (2018) 2852-2864.
[85]	S. Sun, J. Shen, J. Jiang, et al., Targeting ferroptosis opens new avenues for the development of novel therapeutics, Signal. Transduct. Target. Ther. 8 (2023), 372.
[86]	J. Zeng, X. Zhang, Z. Lin, et al., Harnessing ferroptosis for enhanced sarcoma treatment: Mechanisms, progress and prospects, Exp. Hematol. Oncol. 13 (2024), 31.
[87]	Y. Wu, Y. Chen, Research progress on ferroptosis in diabetic kidney disease, Front. Endocrinol. (Lausanne) 13 (2022), 945976.
[88]	Y. Tang, Y. Zhuang, C. Zhao, et al., The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy, Front. Pharmacol. 15 (2024), 1280779.
[89]	Z. Shan, W. Tang, Z. Shi, et al., Ferroptosis: An emerging target for bladder cancer therapy, Curr. Issues. Mol. Biol. 45 (2023) 8201-8214.
[90]	Q. Xu, X. Wen, C. Huang, et al., RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis, Int. J. Surg. 111 (2025) 450-466.
[91]	W. Zhang, B. Jiang, Y. Liu, et al., Bufotalin induces ferroptosis in non-small cell lung cancer cells by facilitating the ubiquitination and degradation of GPX4, Free. Radic. Biol. Med. 180 (2022) 75-84.
[92]	C. Punziano, S. Trombetti, E. Cesaro, et al., Antioxidant systems as modulators of ferroptosis: Focus on transcription factors, Antioxidants (Basel) 13 (2024), 298.
[93]	P. Auberger, C. Favreau, C. Savy, et al., Emerging role of glutathione peroxidase 4 in myeloid cell lineage development and acute myeloid leukemia, Cell. Mol. Biol. Lett. 29 (2024), 98.
[94]	N. Goncalves Ndo, J. Colombo, J.R. Lopes, et al., Effect of melatonin in epithelial mesenchymal transition markers and invasive properties of breast cancer stem cells of canine and human cell lines, PLoS One 11 (2016), e0150407.
[95]	P. Tabnak, Z. HajiEsmailPoor, S. Soraneh, Ferroptosis in lung cancer: From molecular mechanisms to prognostic and therapeutic opportunities, Front. Oncol. 11 (2021), 792827.
[96]	Z. Deng, B. Li, M. Yang, et al., Irradiated microparticles suppress prostate cancer by tumor microenvironment reprogramming and ferroptosis, J Nanobiotechnology 22 (2024), 225.
[97]	L. Ye, X. Wen, J. Qin, et al., Metabolism-regulated ferroptosis in cancer progression and therapy, Cell Death Dis. 15 (2024), 196.
[98]	R. Yan, B. Lin, W. Jin, et al., NRF2, a superstar of ferroptosis, Antioxidants (Basel) 12 (2023), 1739.
[99]	X. Chen, C. Yu, R. Kang, et al., Iron metabolism in ferroptosis, Front. Cell Dev. Biol. 8 (2020), 590226.
[100]	G. Feng, Y. Arima, K. Midorikawa, et al., Knockdown of TFRC suppressed the progression of nasopharyngeal carcinoma by downregulating the PI3K/Akt/mTOR pathway, Cancer Cell Int. 23 (2023), 185.
[101]	Y. Meng, H. Sun, Y. Li, et al., Targeting ferroptosis by ubiquitin system enzymes: A potential therapeutic strategy in cancer, Int. J. Biol. Sci. 18 (2022) 5475-5488.
[102]	H. Kang, F. Meng, F. Liu, et al., Nanomedicines targeting ferroptosis to treat stress-related diseases, Int. J. Nanomedicine 19 (2024) 8189-8210.
[103]	Y. Xiao, Z. Xu, Y. Cheng, et al., Fe3+-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma, Biomater. Res. 27 (2023), 63.
[104]	S. Liu, S. Yan, J. Zhu, et al., Combination RSL3 treatment sensitizes ferroptosis- and EGFR-inhibition-resistant HNSCCs to cetuximab, Int. J. Mol. Sci. 23 (2022), 9014.
[105]	J. Bi, S. Yang, L. Li, et al., Metadherin enhances vulnerability of cancer cells to ferroptosis, Cell Death Dis. 10 (2019), 682.
[106]	M. Jiang, M. Qiao, C. Zhao, et al., Targeting ferroptosis for cancer therapy: Exploring novel strategies from its mechanisms and role in cancers, Transl. Lung Cancer Res. 9 (2020) 1569-1584.
[107]	N. Very, I. El Yazidi-Belkoura, Targeting O-GlcNAcylation to overcome resistance to anti-cancer therapies, Front. Oncol. 12 (2022), 960312.
[108]	Z. Huang, H. Xia, Y. Cui, et al., Ferroptosis: From basic research to clinical therapeutics in hepatocellular carcinoma, J. Clin. Transl. Hepatol. 11 (2023) 207-218.
[109]	A. Mohapatra, A. Mohanty, I.K. Park, Inorganic nanomedicine-mediated ferroptosis: A synergistic approach to combined cancer therapies and immunotherapy, Cancers (Basel) 16 (2024), 3210.
[110]	M.J. Ko, S. Min, H. Hong, et al., Magnetic nanoparticles for ferroptosis cancer therapy with diagnostic imaging, Bioact. Mater. 32 (2024) 66-97.
[111]	X. Fang, Y. Wang, H. Wei, et al., Precision microbiome: A new era of targeted therapy with core probiotics, Research (Wash D C) 8 (2025), 0658.
[112]	D. Xiang, L. Zhou, R. Yang, et al., Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy, Int.J.Nanomedicine. 19 (2024), 2091-2112.
[113]	Y. Chen, Y. Feng, Y. Lin, et al., GSTM3 enhances radiosensitivity of nasopharyngeal carcinoma by promoting radiation-induced ferroptosis through USP14/FASN axis and GPX4, Br. J. Cancer 130 (2024) 755-768.
[114]	Z. Wu, Q. Qu, Mechanism of luteolin induces ferroptosis in nasopharyngeal carcinoma cells, J. Toxicol. Sci. 49 (2024) 399-408.
[115]	S. Huang, B. Cao, J. Zhang, et al., Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: Molecular mechanism and therapeutic potential, Cell Death. Dis. 12 (2021), 237.
[116]	X. Tang, D. Li, Y. Gu, et al., Natural cell based biomimetic cellular transformers for targeted therapy of digestive system cancer, Theranostics. 12 (2022) 7080-7107.
[117]	I. Efimova, E. Catanzaro, L. Van der Meeren, et al., Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity, J. Immunother. Cancer 8 (2020), e001369.
[118]	F. Chen, R. Kang, D. Tang, et al., Ferroptosis: Principles and significance in health and disease, J. Hematol. Oncol. 17 (2024), 41.
[119]	D. Tang, G. Kroemer, R. Kang, Ferroptosis in immunostimulation and immunosuppression, Immunol. Rev. 321 (2024) 199-210.
[120]	M.F. Wang, J. Guo, S.J. Yuan, et al., Targeted sonodynamic therapy induces tumor cell quasi-immunogenic ferroptosis and macrophage immunostimulatory autophagy in glioblastoma, Biomaterials 315 (2025), 122913.
[121]	Q. Zhou, Y. Meng, D. Li, et al., Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies, Signal. Transduct. Target. Ther. 9 (2024), 55.
[122]	T. Yun, Z. Liu, J. Wang, et al., Microenvironment immune response induced by tumor ferroptosis-the application of nanomedicine, Front Oncol. 12 (2022), 1019654.
[123]	C. Sun, J. Zhan, Y. Li, et al., Non-apoptotic regulated cell death mediates reprogramming of the tumour immune microenvironment by macrophages, J. Cell Mol. Med. 28 (2024), e18348.
[124]	P. Tao, B. Su, X. Mao, et al., Interleukin-35 inhibits NETs to ameliorate Th17/Treg immune imbalance during the exacerbation of cigarette smoke exposed-asthma via gp130/STAT3/ferroptosis axis, Redox. Biol. 82 (2025), 103594.
[125]	Z. Wang, H. Zhang, L. Wang, et al., Bibliometric analysis of ferroptosis: A comprehensive evaluation of its contribution to cancer immunity and immunotherapy, Front. Oncol. 13 (2023), 1183405.
[126]	Y. Li, X. Cheng, Enhancing colorectal cancer immunotherapy: The pivotal role of ferroptosis in modulating the tumor microenvironment, Int. J. Mol. Sci. 25 (2024), 9141.
[127]	Y. Zheng, L. Sun, J. Guo, et al., The crosstalk between ferroptosis and anti-tumor immunity in the tumor microenvironment: Molecular mechanisms and therapeutic controversy, Cancer. Commun (Lond) 43 (2023) 1071-1096.
[128]	M. Wang, F. Yu, Y. Zhang, et al., Programmed cell death in tumor immunity: Mechanistic insights and clinical implications, Front. Immunol. 14 (2023), 1309635.
[129]	H. Wang, Y. Liu, S. Che, et al., Deciphering the link: ferroptosis and its role in glioma, Front. Immunol. 15 (2024), 1346585.
[130]	Y. Hua, S. Yang, Y. Zhang, et al., Modulating ferroptosis sensitivity: environmental and cellular targets within the tumor microenvironment, J.Exp.Clin.Cancer.Res. 43 (2024), 19.
[131]	X. Gu, Y. Liu, X. Dai, et al., Deciphering the potential roles of ferroptosis in regulating tumor immunity and tumor immunotherapy, Front. Immunol. 14 (2023), 1137107.
[132]	C. Qian, C. Liu, W. Liu, et al., Targeting vascular normalization: A promising strategy to improve immune-vascular crosstalk in cancer immunotherapy, Front. Immunol. 14 (2023), 1291530.
[133]	Z. Li, S. Chen, X. He, et al., SLC3A2 promotes tumor-associated macrophage polarization through metabolic reprogramming in lung cancer, Cancer. Sci. 114 (2023) 2306-2317.
[134]	Q. Bi, Z.J. Sun, J.Y. Wu, et al., Ferroptosis-mediated formation of tumor-promoting immune microenvironment, Front. Oncol. 12 (2022), 868639.
[135]	K. Jia, Y. Zhang, F. Li, et al., Acteoside ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injury via targeting PCBP2, Acta. Pharm. Sin. B. 15 (2025) 2077-2094.
[136]	T. Liu, C. Zhu, X. Chen, et al., Ferroptosis, as the most enriched programmed cell death process in glioma, induces immunosuppression and immunotherapy resistance, Neuro. Oncol. 24 (2022) 1113-1125.
[137]	J. Ma, H. Yuan, J. Zhang, et al., An ultrasound-activated nanoplatform remodels tumor microenvironment through diverse cell death induction for improved immunotherapy, J. Control. Release 370 (2024) 501-515.
[138]	Y. Lv, P. Zheng, Y. Mao, et al., Intratumor APOL3 delineates a distinctive immunogenic ferroptosis subset with prognosis prediction in colorectal cancer, Cancer Sci. 115 (2024) 257-269.
[139]	Z. Cheng, C. Xue, M. Liu, et al., Injectable microenvironment-responsive hydrogels with redox-activatable supramolecular prodrugs mediate ferroptosis-immunotherapy for postoperative tumor treatment, Acta Biomater. 169 (2023) 289-305.