# Inducing Ferroptosis: Sensitization Strategy for Radiotherapy and Its Application

**Authors:** Xun Chen, Shangwu Chen, Dongsheng Yu, Wei Zhao

PMC · DOI: 10.3390/antiox15020237 · Antioxidants · 2026-02-11

## TL;DR

This review explores how inducing ferroptosis, a type of cell death, can improve the effectiveness of cancer radiotherapy.

## Contribution

The paper provides a comprehensive analysis of ferroptosis as a radiosensitization strategy and outlines its mechanisms and future directions.

## Key findings

- Ionizing radiation in radiotherapy can induce ferroptosis in tumor cells.
- Combining radiotherapy with ferroptosis induction enhances tumor cell sensitivity to treatment.
- The review highlights current strategies and identifies gaps in ferroptosis-based radiosensitization.

## Abstract

Ferroptosis is a novel regulated cell death caused by the accumulation of iron-dependent ROS and excessive local lipid peroxides in the membrane, widely involved in various physiological and pathological processes. Ferroptosis has emerged as a key mechanism in radiotherapy response. Radiotherapy is an effective treatment for many types of cancers, which not only causes double-stranded DNA break-induced apoptosis, but also induces the production of ROS, leading to oxidative stress and tumor cell death. Recent studies have shown that ionizing radiation in radiotherapy can induce ferroptosis in tumor cells. The combination of radiotherapy and ferroptosis induction can synergistically induce ferroptosis to enhance the sensitivity of tumor cells to radiotherapy, making ferroptosis induction a promising radiosensitization strategy. In this review, we summarize the characteristics and regulation of ferroptosis, analyze the mechanism of radiotherapy-induced ferroptosis, and specifically discuss the different strategies of inducing ferroptosis for radiosensitization. We also point out the shortcomings, future prospects, and research directions of this strategy.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** Gpx4 (glutathione peroxidase 4) [NCBI Gene 625249] {aka GPx-4, GSHPx-4, PHGPx, mtPHGPx, snGPx}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, ACSL4 (acyl-CoA synthetase long chain family member 4) [NCBI Gene 2182] {aka ACS4, FACL4, LACS4, MRX63, MRX68, XLID63}, ME1 (malic enzyme 1) [NCBI Gene 4199] {aka HUMNDME, MES}, Slc3a2 (solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2) [NCBI Gene 17254] {aka 4F2, 4F2HC, Cd98, Ly-10, Ly-m10, Ly10}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Apoc1 (apolipoprotein C-I) [NCBI Gene 11812] {aka Apo-CIB, ApoC-IB, apo-CI, apoC-I}, KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, TFRC (transferrin receptor) [NCBI Gene 7037] {aka CD71, IMD46, T9, TFR, TFR1, TR}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, SLC3A2 (solute carrier family 3 member 2) [NCBI Gene 6520] {aka 4F2, 4F2HC, 4T2HC, CD98, CD98HC, MDU1}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, GRK1 (G protein-coupled receptor kinase 1) [NCBI Gene 6011] {aka GPRK1, RHOK, RK}, IL9 (interleukin 9) [NCBI Gene 3578] {aka HP40, IL-9, P40}, SLC1A5 (solute carrier family 1 member 5) [NCBI Gene 6510] {aka AAAT, ASCT2, ATBO, M7V1, M7VS1, R16}, FGF5 (fibroblast growth factor 5) [NCBI Gene 2250] {aka HBGF-5, Smag-82, TCMGLY}, POR (cytochrome p450 oxidoreductase) [NCBI Gene 5447] {aka CPR, CYPOR, P450R}, ACSL3 (acyl-CoA synthetase long chain family member 3) [NCBI Gene 2181] {aka ACS3, FACL3, LACS 3, LACS3, PRO2194}, DEPDC5 (DEP domain containing 5, GATOR1 subcomplex subunit) [NCBI Gene 9681] {aka DEE111, DEP.5, FFEVF, FFEVF1, FPEVF}, LPCAT3 (lysophosphatidylcholine acyltransferase 3) [NCBI Gene 10162] {aka C3F, LPCAT, LPLAT 5, LPLAT12, LPSAT, MBOAT5}, TGM2 (transglutaminase 2) [NCBI Gene 7052] {aka G(h), TG(C), TGC, hTG2, tTG}, Acsl4 (acyl-CoA synthetase long-chain family member 4) [NCBI Gene 50790] {aka 9430020A05Rik, ACS4, Facl4, Lacs4}, TXNRD1 (thioredoxin reductase 1) [NCBI Gene 7296] {aka GRIM-12, TR, TR1, TRXR1, TXNR, TXNR1}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, CD47 (CD47 molecule) [NCBI Gene 961] {aka IAP, MER6, OA3}, GSS (glutathione synthetase) [NCBI Gene 2937] {aka CNSHA6, GSHS, HEL-S-64p, HEL-S-88n}, Ano1 (anoctamin 1, calcium activated chloride channel) [NCBI Gene 101772] {aka Tmem16a}, DHODH (dihydroorotate dehydrogenase (quinone)) [NCBI Gene 1723] {aka DHOdehase, POADS, URA1}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, COX8A (cytochrome c oxidase subunit 8A) [NCBI Gene 1351] {aka COX, COX8, COX8-2, COX8L, MC4DN15, VIII}, APOC1 (apolipoprotein C1) [NCBI Gene 341] {aka APOC1B, Apo-CI, ApoC-I, apo-CIB, apoC-IB}, PRDX5 (peroxiredoxin 5) [NCBI Gene 25824] {aka ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20}, Cgas (cyclic GMP-AMP synthase) [NCBI Gene 214763] {aka E330016A19Rik, Mb21d1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Sting1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 72512] {aka 2610307O08Rik, ERIS, MPYS, Mita, STING, STING-beta}, DECR1 (2,4-dienoyl-CoA reductase 1) [NCBI Gene 1666] {aka DECR, NADPH, SDR18C1}, FOXM1 (forkhead box M1) [NCBI Gene 2305] {aka FKHL16, FOXM1A, FOXM1B, FOXM1C, HFH-11, HFH11}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, ANXA3 (annexin A3) [NCBI Gene 306] {aka ANX3}, ALOX5 (arachidonate 5-lipoxygenase) [NCBI Gene 240] {aka 5-LO, 5-LOX, 5LPG, LOG5}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, SLC7A11 (solute carrier family 7 member 11) [NCBI Gene 23657] {aka CCBR1, xCT}, SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, ELF4 (E74 like ETS transcription factor 4) [NCBI Gene 2000] {aka AIFBL2, ELFR, MEF}, Fgf5 (fibroblast growth factor 5) [NCBI Gene 14176] {aka Fgf-5, Fgf3a, HBGF-5, angora, go}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, SOD2 (superoxide dismutase 2) [NCBI Gene 6648] {aka GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6}, HDAC6 (histone deacetylase 6) [NCBI Gene 10013] {aka CPBHM, HD6, JM21, KDAC6, PPP1R90}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, OTUB1 (OTU deubiquitinase, ubiquitin aldehyde binding 1) [NCBI Gene 55611] {aka HSPC263, OTB1, OTU1}, IRF1 (interferon regulatory factor 1) [NCBI Gene 3659] {aka IMD117, IRF-1, MAR}, Slc7a11 (solute carrier family 7 (cationic amino acid transporter, y+ system), member 11) [NCBI Gene 26570] {aka 9930009M05Rik, sut, xCT}, Atl1 (atlastin GTPase 1) [NCBI Gene 73991] {aka 4930435M24Rik, Adfsp, Fsp1, Spg3, Spg3a}
- **Diseases:** acidosis (MESH:D000138), cytotoxicity (MESH:D064420), bone marrow impairment (MESH:D001855), von Hippel-Lindau (MESH:D006623), synovial sarcoma (MESH:D013584), colorectal cancer (MESH:D015179), Ferroptotic Cell Death (MESH:D003643), metastases (MESH:D009362), rheumatoid arthritis (MESH:D001172), embryonic lethality (MESH:D020964), NPC (MESH:D000077274), clear cell renal cell carcinoma (MESH:D002292), necrosis (MESH:D009336), ESCC (MESH:D004938), hepatocellular carcinoma (MESH:D006528), malaria infections (MESH:D008288), liver and kidney damage (MESH:D056486), breast cancer (MESH:D001943), inflammatory bowel disease (MESH:D015212), retinoblastoma 1 (MESH:D012175), lung injury (MESH:D055370), esophageal squamous cell carcinoma (MESH:D000077277), hepatic fibrosis (MESH:D008103), FINs (MESH:D000092582), Tumor (MESH:D009369), prostate cancer (MESH:D011471), glioma (MESH:D005910), injury to (MESH:D014947), NSCLC (MESH:D002289), HNSCC (MESH:D000077195), tumorigenesis (MESH:D063646), cachexia (MESH:D002100), hypoxic (MESH:D002534), gastric cancer (MESH:D013274)
- **Chemicals:** phosphatidylcholine (MESH:D010713), fatty acid (MESH:D005227), malondialdehyde (MESH:D008315), MUFAs (MESH:D005229), FAD (MESH:D005182), GSSG (MESH:D019803), peroxides (MESH:D010545), acyl-CoA (MESH:D000214), Ginsenoside RK1 (MESH:C472077), Erastin (MESH:C477224), cystine (MESH:D003553), L-carnitine (MESH:D002331), PUFA (MESH:D005231), Sulfasalazine (MESH:D012460), PE (MESH:C483858), FIN (-), H2O2 (MESH:D006861), cisplatin (MESH:D002945), ROS (MESH:D017382), peroxyl radicals (MESH:C049375), ML210 (MESH:C000718731), ubiquinol (MESH:C003741), beta-Elemene (MESH:C445979), Oleic acid (MESH:D019301), AGuIX (MESH:C000714949), ubiquinone (MESH:D014451), Cys (MESH:D003545), Lipid (MESH:D008055), glutamine (MESH:D005973), Cobalt (MESH:D003035), GSH (MESH:D005978), PEs (MESH:D010714), quinoline (MESH:C037219), Tubastatin A (MESH:C553587), bupivacaine (MESH:D002045), CoQ10 (MESH:C024989), carbon (MESH:D002244), lipid hydroperoxides (MESH:D008054), Triacsin C (MESH:C034613), oxygen (MESH:D010100), BIBR1532 (MESH:C458523), linoleate (MESH:D019787), Mefloquine (MESH:D015767), Dihydroartemisinin (MESH:C039060), 6-hydroxy-FAD (MESH:C052277), hemin (MESH:D006427), Hyaluronic acid (MESH:D006820), hydroxyl radicals (MESH:D017665), cholesterol (MESH:D002784), ethanol (MESH:D000431), 4-hydroxynonenal (MESH:C027576), Glu (MESH:D018698), sorafenib (MESH:D000077157), malonyl-CoA (MESH:D008316), PGE2 (MESH:D015232), 7-dehydrocholesterol (MESH:C016705), AA (MESH:D016718), Iron (MESH:D007501), linolenate (MESH:D017962), phospholipid (MESH:D010743)
- **Species:** Homo sapiens (human, species) [taxon 9606], Curcuma zedoaria (species) [taxon 136224], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Panax ginseng (Asiatic ginseng, species) [taxon 4054], C. elegans [taxon 328850]
- **Cell lines:** CDX — Mus musculus (Mouse), Hybridoma (CVCL_KD04)

## Full text

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## Figures

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## References

158 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938210/full.md

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Source: https://tomesphere.com/paper/PMC12938210