{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:41:24Z","timestamp":1791380484138,"version":"4.3.3"},"reference-count":132,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Locally advanced rectal cancer is commonly treated using total neoadjuvant therapy (TNT), which integrates radiotherapy with systemic chemotherapy to improve tumor downstaging, local control, and long-term oncologic outcomes. Despite its central role in treatment, responses to radiotherapy remain highly heterogeneous. While some tumors undergo complete regression, others exhibit intrinsic or acquired treatment resistance, resulting in incomplete tumor control while experiencing treatment-related toxicity. Understanding the biological determinants that govern radiation sensitivity in rectal cancer, therefore, represents a major clinical challenge. Ionizing radiation induces tumor cell death primarily through the generation of reactive oxygen species (ROS) and DNA damage, particularly DNA double-strand breaks. In addition to nuclear DNA injury, radiation-induced oxidative stress can initiate lipid peroxidation within cellular membranes. When lipid peroxide accumulation exceeds the capacity of cellular antioxidant systems, this process can trigger ferroptosis, an iron-dependent form of regulated cell death driven by phospholipid oxidation. Ferroptotic susceptibility is regulated by interconnected metabolic pathways, including cystine transport through system Xc\u2212 (SLC7A11\/SLC3A2), glutathione synthesis, glutathione peroxidase-4 (GPX4) activity, iron metabolism, and membrane lipid remodeling. Recent evidence further indicates that ferroptosis intersects with antitumor immunity. Ferroptotic tumor cells release oxidized lipid mediators and damage-associated molecular signals that can influence immune activation, while interferon-\u03b3 produced by activated CD8+ T cells during immune checkpoint blockade suppresses SLC7A11 expression, limiting cystine uptake and promoting ferroptotic tumor cell death. These findings suggest that ferroptosis represents a mechanistic interface between tumor metabolic vulnerability and immune-mediated cytotoxicity. This interaction is particularly relevant in colorectal cancer biology, where immune checkpoint inhibitors demonstrate clinical benefit primarily in tumors with deficient mismatch repair or microsatellite instability-high (MSI-H) status. The vast majority of rectal cancers are microsatellite stable (MSS) and exhibit limited responsiveness to immunotherapy due to reduced immunogenicity and immune exclusion within the tumor microenvironment. Strategies capable of increasing tumor immunogenicity in this setting are therefore of considerable interest. In this review, we examine the molecular mechanisms linking radiation-induced oxidative stress to ferroptosis and tumor immunity in colorectal cancer, while focusing on the clinical context of radiotherapy in rectal cancer. We discuss how lipid metabolism, iron homeostasis, cysteine-dependent antioxidant systems, and immune signaling pathways converge to regulate ferroptotic vulnerability and radiation response. We further explore the therapeutic potential of integrating radiotherapy, ferroptosis-targeting strategies, and immunotherapy to overcome radioresistance and improve treatment outcomes in colorectal cancer.<\/jats:p>","DOI":"10.3390\/cells15110993","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:09:07Z","timestamp":1779970147000},"page":"993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting Ferroptosis to Overcome Radioresistance and Enhance Immunotherapy in Colorectal Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0458-8102","authenticated-orcid":false,"given":"Sara","family":"Soltani Tehrani","sequence":"first","affiliation":[{"name":"The Ohio State University James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Division of Colon and Rectal Surgery, Department of Surgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Isaac","family":"Olson","sequence":"additional","affiliation":[{"name":"The Ohio State University James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Division of Colon and Rectal Surgery, Department of Surgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karishma","family":"Kundu","sequence":"additional","affiliation":[{"name":"The Ohio State University James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Division of Colon and Rectal Surgery, Department of Surgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Ferrandon","sequence":"additional","affiliation":[{"name":"The Ohio State University James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Division of Colon and Rectal Surgery, Department of Surgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew F.","family":"Kalady","sequence":"additional","affiliation":[{"name":"The Ohio State University James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Division of Colon and Rectal Surgery, Department of Surgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Siegel, R.L., Wagle, N.S., Star, J., Kratzer, T.B., Smith, R.A., and Jemal, A. (2026). Colorectal cancer statistics, 2026. CA Cancer J. Clin., 76.","DOI":"10.3322\/caac.70067"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sawicki, T., Ruszkowska, M., Danielewicz, A., Nied\u017awiedzka, E., Ar\u0142ukowicz, T., and Przyby\u0142owicz, K.E. (2021). A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers, 13.","DOI":"10.3390\/cancers13092025"},{"key":"ref_3","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.annonc.2024.06.019","article-title":"Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: Long-term results of the UNICANCER-PRODIGE 23 trial","volume":"35","author":"Conroy","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1200\/JCO.22.00032","article-title":"Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy","volume":"40","author":"Patil","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/DCR.0000000000000266","article-title":"American Joint Committee on Cancer and College of American Pathologists Regression Grade","volume":"58","author":"Mace","year":"2015","journal-title":"Dis. Colon Rectum"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1200\/JCO.2011.37.7176","article-title":"Wait-and-See Policy for Clinical Complete Responders After Chemoradiation for Rectal Cancer","volume":"29","author":"Maas","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Park, B., Lee, S., Jo, I., Kang, D., Kim, T., Ryu, J., Kong, H., Baek, M., and Ahn, T. (2025). Mechanistic Insights into Radiation Resistance in Colorectal Cancer: Gene Exploration Study. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083849"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.4161\/cbt.8.21.9988","article-title":"Modulating the tumor microenvironment to increase radiation responsiveness","volume":"8","author":"Karar","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Span, P.N., and Bussink, J. (2019). The Role of Hypoxia and the Immune System in Tumor Radioresistance. Cancers, 11.","DOI":"10.3390\/cancers11101555"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jia, B., Li, J., Song, Y., and Luo, C. (2023). ACSL4-Mediated Ferroptosis and Its Potential Role in Central Nervous System Diseases and Injuries. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210021"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1016\/j.immuni.2024.08.003","article-title":"PD-1 signaling limits expression of phospholipid phosphatase 1 and promotes intratumoral CD8+ T cell ferroptosis","volume":"57","author":"Ping","year":"2024","journal-title":"Immunity"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41422-019-0263-3","article-title":"The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression","volume":"30","author":"Lei","year":"2020","journal-title":"Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1007\/s13238-021-00841-y","article-title":"Ferroptosis, radiotherapy, and combination therapeutic strategies","volume":"12","author":"Lei","year":"2021","journal-title":"Protein Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1089\/ars.2008.2270","article-title":"Regulation of Autophagy by Reactive Oxygen Species (ROS): Implications for Cancer Progression and Treatment","volume":"11","author":"Azad","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1056\/NEJMoa2201445","article-title":"PD-1 Blockade in Mismatch Repair\u2013Deficient, Locally Advanced Rectal Cancer","volume":"386","author":"Cercek","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40659-019-0241-8","article-title":"Psoralen inhibits malignant proliferation and induces apoptosis through triggering endoplasmic reticulum stress in human SMMC7721 hepatoma cells","volume":"52","author":"Wang","year":"2019","journal-title":"Biol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Storozynsky, Q., and Hitt, M.M. (2020). The Impact of Radiation-Induced DNA Damage on cGAS-STING-Mediated Immune Responses to Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228877"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41392-020-0150-x","article-title":"DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer","volume":"5","author":"Huang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1080\/09553002.2017.1287454","article-title":"Effects of ionizing radiation on DNA methylation: From experimental biology to clinical applications","volume":"93","author":"Miousse","year":"2017","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2011.12.012","article-title":"Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury","volume":"327","author":"Azzam","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1021\/acschembio.9b00939","article-title":"Radiation-Induced Lipid Peroxidation Triggers Ferroptosis and Synergizes with Ferroptosis Inducers","volume":"15","author":"Ye","year":"2020","journal-title":"ACS Chem. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103286","DOI":"10.1016\/j.redox.2024.103286","article-title":"Hypoxia-induced cysteine metabolism reprogramming is crucial for the tumorigenesis of colorectal cancer","volume":"75","author":"Lin","year":"2024","journal-title":"Redox Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, F.-J., Long, H.-Z., Zhou, Z.-W., Luo, H.-Y., Xu, S.-G., and Gao, L.-C. (2022). System Xc\u2212\/GSH\/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.910292"},{"key":"ref_28","first-page":"1","article-title":"Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy","volume":"7","author":"Gao","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of Ferroptotic Cancer Cell Death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00018-025-05958-5","article-title":"Ferroptosis inhibitors: Mechanisms of action and therapeutic potential","volume":"82","author":"Duo","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/s41586-019-1705-2","article-title":"The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis","volume":"575","author":"Bersuker","year":"2019","journal-title":"Nature"},{"key":"ref_32","first-page":"1","article-title":"Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies","volume":"9","author":"Zhou","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","first-page":"1","article-title":"DHODH tangoing with GPX4 on the ferroptotic stage","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41586-021-03539-7","article-title":"DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer","volume":"593","author":"Mao","year":"2021","journal-title":"Nature"},{"key":"ref_35","first-page":"1","article-title":"In defence of ferroptosis","volume":"10","author":"Alves","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, J., and Roh, J.-L. (2025). Dihydroorotate Dehydrogenase in Mitochondrial Ferroptosis and Cancer Therapy. Cells, 14.","DOI":"10.3390\/cells14231889"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41420-021-00579-w","article-title":"Ferroptosis: A cell death connecting oxidative stress, inflammation and cardiovascular diseases","volume":"7","author":"Yu","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1097\/HP.0000000000001601","article-title":"Radiation-induced Cell Death and Its Mechanisms","volume":"123","author":"Jiao","year":"2022","journal-title":"Heal. Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/s41418-019-0393-7","article-title":"Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism","volume":"27","author":"Chen","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition","volume":"13","author":"Doll","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.bbagen.2008.09.004","article-title":"Ferritins: A family of molecules for iron storage, antioxidation and more","volume":"1790","author":"Arosio","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Gen. Subj."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.3324\/haematol.2019.224899","article-title":"Transferrin receptor 1-mediated iron uptake plays an essential role in hematopoiesis","volume":"105","author":"Wang","year":"2019","journal-title":"Haematologica"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.immuni.2024.03.019","article-title":"Ironing out the role of ferroptosis in immunity","volume":"57","author":"Bell","year":"2024","journal-title":"Immunity"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Santana-Codina, N., and Mancias, J.D. (2018). The Role of NCOA4-Mediated Ferritinophagy in Health and Disease. Pharmaceuticals, 11.","DOI":"10.20944\/preprints201809.0148.v1"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1080\/15548627.2016.1187366","article-title":"Autophagy promotes ferroptosis by degradation of ferritin","volume":"12","author":"Hou","year":"2016","journal-title":"Autophagy"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature13148","article-title":"Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy","volume":"509","author":"Mancias","year":"2014","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2303484","DOI":"10.1002\/advs.202303484","article-title":"Inhibition of CARM1-Mediated Methylation of ACSL4 Promotes Ferroptosis in Colorectal Cancer","volume":"10","author":"Feng","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.cell.2024.01.030","article-title":"Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis","volume":"187","author":"Qiu","year":"2024","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"32433","DOI":"10.1073\/pnas.2006828117","article-title":"Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer","volume":"117","author":"Lee","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1093\/gastro\/goab034","article-title":"Comparison of guidelines on rectal cancer: Exception proves the rule?","volume":"9","author":"Dou","year":"2021","journal-title":"Gastroenterol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"111194","DOI":"10.1016\/j.radonc.2025.111194","article-title":"Short-course radiotherapy versus long-course chemoradiotherapy in total neoadjuvant therapy of rectal cancer \u2013 A multicenter analysis of early outcomes and toxicity","volume":"213","author":"Wurschi","year":"2025","journal-title":"Radiother. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2147\/OTT.S474855","article-title":"Prognostic Value of Pretreatment Carcinoembryonic Antigen (CEA) in Rectal Cancer Treated with Preoperative Short-Course Radiotherapy with Delayed Surgery or Long-Course Radiotherapy","volume":"ume 18","author":"Lin","year":"2025","journal-title":"OncoTargets Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1158\/1078-0432.CCR-25-2733","article-title":"Differential Immunologic Effects of Short-Course and Long-Course Radiotherapy in Locally Advanced Rectal Cancer","volume":"32","author":"Hillson","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1200\/JCO.23.01208","article-title":"Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial","volume":"42","author":"Verheij","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.yasu.2021.05.007","article-title":"Watch-and-wait Management for Rectal Cancer After Clinical Complete Response to Neoadjuvant Therapy","volume":"55","author":"Yuval","year":"2021","journal-title":"Adv. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13515","DOI":"10.18632\/aging.202774","article-title":"Suppressing the KIF20A\/NUAK1\/Nrf2\/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin","volume":"13","author":"Yang","year":"2021","journal-title":"Aging"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-025-07226-3","article-title":"Fusobacterium nucleatum enhances oxaliplatin resistance in colon cancer by increasing PVT1 expression","volume":"23","author":"Gao","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.freeradbiomed.2024.04.226","article-title":"Fusobacterium nucleatum induces oxaliplatin resistance by inhibiting ferroptosis through E-cadherin\/\u03b2-catenin\/GPX4 axis in colorectal cancer","volume":"220","author":"Li","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12935-025-03753-7","article-title":"Multiomic traits reveal that critical irinotecan-related core regulator FSTL3 promotes CRC progression and affects ferroptosis","volume":"25","author":"Huang","year":"2025","journal-title":"Cancer Cell Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"199","DOI":"10.4103\/jcrt.jcrt_225_22","article-title":"Modified FOLFIRINOX (mFOLFIRINOX) as neoadjuvant therapy and \u2018salvage\u2019 in patients with high risk locally advanced rectal cancers \u2013 tolerance and early outcomes","volume":"20","author":"Prajapati","year":"2023","journal-title":"J. Cancer Res. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ochiai, K., Bhutiani, N., Ikeda, A., Uppal, A., White, M.G., Peacock, O., Messick, C.A., Bednarski, B.K., You, Y.-Q.N., and Skibber, J.M. (2024). Total Neoadjuvant Therapy for Rectal Cancer: Which Regimens to Use?. Cancers, 16.","DOI":"10.3390\/cancers16112093"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"891","DOI":"10.3349\/ymj.2025.0216","article-title":"Long-Term Outcomes of Long-Course Chemoradiotherapy vs. Short-Course Radiotherapy Followed by Consolidation Chemotherapy in Rectal Cancer","volume":"66","author":"Lee","year":"2025","journal-title":"Yonsei Med. J."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Koukourakis, I.M., Xanthopoulou, E., Koukourakis, M.I., Tiniakos, D., Kouloulias, V., and Zygogianni, A. (2024). IFN-Type-I Response and Systemic Immunity in Rectal Adenocarcinoma Patients Treated with Conventional or Hypofractionated Neoadjuvant Radiotherapy. Biomolecules, 14.","DOI":"10.3390\/biom14040448"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"100043","DOI":"10.1016\/j.soi.2024.100043","article-title":"Assessing the OPRA trial for surgical oncologists: Safety and feasibility of a total neoadjuvant therapy approach in patients with rectal cancer","volume":"1","author":"Zambare","year":"2024","journal-title":"Surg. Oncol. Insight"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Hu, B., Yin, Y., Li, S., and Guo, X. (2022). Insights on Ferroptosis and Colorectal Cancer: Progress and Updates. Molecules, 28.","DOI":"10.3390\/molecules28010243"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.20517\/cdr.2024.151","article-title":"Ferroptosis-related signaling pathways in cancer drug resistance","volume":"8","author":"Yang","year":"2025","journal-title":"Cancer Drug Resist."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1158\/2159-8290.CD-19-0338","article-title":"Radiotherapy and Immunotherapy Promote Tumoral Lipid Oxidation and Ferroptosis via Synergistic Repression of SLC7A11","volume":"9","author":"Lang","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_68","first-page":"CD014718","article-title":"Molecular biomarkers for predicting complete response to preoperative chemoradiation in people with locally advanced rectal cancer","volume":"2024","author":"Lord","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Li, M., Xiao, Q., Venkatachalam, N., Hofheinz, R.-D., Veldwijk, M.R., Herskind, C., Ebert, M.P., and Zhan, T. (2022). Predicting response to neoadjuvant chemoradiotherapy in rectal cancer: From biomarkers to tumor models. Ther. Adv. Med. Oncol., 14.","DOI":"10.1177\/17588359221077972"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Manca, P., Chen, C.-T., Shah, F., Lee, C., Domenico, D., Omer, D., Gonzalez, S., De Bruijn, I., Ahuno, S., and Chatila, W.K. (2025). Ultrasensitive ctDNA monitoring for organ preservation in patients with locally advanced rectal cancer. npj Precis. Oncol., 10.","DOI":"10.1038\/s41698-025-01208-w"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"869","DOI":"10.12998\/wjcc.v6.i15.869","article-title":"Biomarkers in colorectal cancer: Current clinical utility and future perspectives","volume":"6","author":"Vacante","year":"2018","journal-title":"World J. Clin. Cases"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Kerkhove, L., Geirnaert, F., Coppens, J., Guti\u00e9rrez, A., Vandenplas, H., Gevaert, T., Dufait, I., and De Ridder, M. (2025). Ferroptosis is a Pivotal Player in Radiation-induced Cell Death of Colorectal Cancer Cells. Radiat. Res., 205.","DOI":"10.1667\/RADE-24-00251.1"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Chen, X., Chen, S., Yu, D., and Zhao, W. (2026). Inducing Ferroptosis: Sensitization Strategy for Radiotherapy and Its Application. Antioxidants, 15.","DOI":"10.3390\/antiox15020237"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e36446","DOI":"10.1016\/j.heliyon.2024.e36446","article-title":"Improving the efficacy of immunotherapy for colorectal cancer: Targeting tumor microenvironment-associated immunosuppressive cells","volume":"10","author":"Zou","year":"2024","journal-title":"Heliyon"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.3748\/wjg.v30.i13.1815","article-title":"Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer: Unravelling challenges and future directions","volume":"30","author":"Sharma","year":"2024","journal-title":"World J. Gastroenterol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5924","DOI":"10.1038\/s44318-025-00569-z","article-title":"Decoding immunometabolism with next-generation tools: Lessons from dendritic cells and T cells","volume":"44","author":"Wang","year":"2025","journal-title":"EMBO J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5253","DOI":"10.1038\/s41388-021-01946-8","article-title":"DCision-making in tumors governs T cell anti-tumor immunity","volume":"40","author":"Alfei","year":"2021","journal-title":"Oncogene"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-019-1170-y","article-title":"CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy","volume":"569","author":"Wang","year":"2019","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ccell.2022.02.003","article-title":"CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4","volume":"40","author":"Liao","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/or.2022.8308","article-title":"IFN\u03b3 enhances ferroptosis by increasing JAK-STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma","volume":"47","author":"Yu","year":"2022","journal-title":"Oncol. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1862949","DOI":"10.1080\/2162402X.2020.1862949","article-title":"Ferroptosis becomes immunogenic: Implications for anticancer treatments","volume":"10","author":"Tang","year":"2020","journal-title":"OncoImmunology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.bbrc.2019.01.090","article-title":"The release and activity of HMGB1 in ferroptosis","volume":"510","author":"Wen","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-022-31218-2","article-title":"Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity","volume":"13","author":"Wiernicki","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Jia, H., Zhou, L.-Q., Wen, R.-B., Yu, Y., Wang, N., Zhang, T.-S., Peng, Z.-Y., Chen, J.-F., Yu, G.-Y., and Zhang, W. (2026). Reengineering immunotherapeutic responses: Ferroptosis-primed radiotherapy converts cold-colorectal tumors into immunotherapy checkpoint inhibitor-sensitive hot lesions. LabMed Discov., 3.","DOI":"10.1016\/j.lmd.2026.100119"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.immuni.2021.05.003","article-title":"Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors","volume":"54","author":"Xu","year":"2021","journal-title":"Immunity"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Cai, H., Ren, Y., Chen, S., Wang, Y., and Chu, L. (2023). Ferroptosis and tumor immunotherapy: A promising combination therapy for tumors. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1119369"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13014-023-02335-z","article-title":"Role of the cGAS-STING pathway in radiotherapy for non-small cell lung cancer","volume":"18","author":"Yang","year":"2023","journal-title":"Radiat. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/s12276-020-0416-y","article-title":"The cGAS\/STING\/TBK1\/IRF3 innate immunity pathway maintains chromosomal stability through regulation of p21 levels","volume":"52","author":"Basit","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.immuni.2014.10.019","article-title":"STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors","volume":"41","author":"Deng","year":"2014","journal-title":"Immunity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00262-013-1506-7","article-title":"Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8+ T cells","volume":"63","author":"Lim","year":"2013","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1080\/15548627.2019.1582973","article-title":"Radiation induces EIF2AK3\/PERK and ERN1\/IRE1 mediated pro-survival autophagy","volume":"15","author":"Chaurasia","year":"2019","journal-title":"Autophagy"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1172\/JCI69219","article-title":"Radiation and immunotherapy: A synergistic combination","volume":"123","author":"Kalbasi","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_93","first-page":"1639","article-title":"The High Expression of SLC7A11 and GPX4 are Significantly Correlated with \u03b2-Catenin in Colorectal Cancer","volume":"ume 16","author":"Ou","year":"2024","journal-title":"Cancer Manag. Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Sui, X., Zhang, R., Liu, S., Duan, T., Zhai, L., Zhang, M., Han, X., Xiang, Y., Huang, X., and Lin, H. (2018). RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01371"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/OTT.S569536","article-title":"The Dual Role of SLC7A11 in Colorectal Cancer Ferroptosis: From Molecular Mechanisms to Therapeutic Opportunities","volume":"ume 19","author":"Hu","year":"2026","journal-title":"OncoTargets Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"104305","DOI":"10.3748\/wjg.v31.i16.104305","article-title":"LncRNA FTX promotes colorectal cancer radioresistance through disturbing redox balance and inhibiting ferroptosis via miR-625-5p\/SCL7A11 axis","volume":"31","author":"Dai","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"103950","DOI":"10.1016\/j.redox.2025.103950","article-title":"Artemisitene triggers calcium-dependent ferroptosis by disrupting the LSH-EWSR1 interaction in colorectal cancer","volume":"89","author":"Zhu","year":"2025","journal-title":"Redox Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-025-08146-2","article-title":"USP5 regulates ferroptosis in colorectal cancer by targeting the YBX3\/SLC7A11 axis through lysosomal degradation","volume":"16","author":"Qiu","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zhang, X., Ma, Y., Ma, J., Yang, L., Song, Q., Wang, H., and Lv, G. (2022). Glutathione Peroxidase 4 as a Therapeutic Target for Anti-Colorectal Cancer Drug-Tolerant Persister Cells. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.913669"},{"key":"ref_100","first-page":"84","article-title":"How erastin assassinates cells by ferroptosis revealed","volume":"14","author":"Gan","year":"2022","journal-title":"Protein Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/nchembio.2079","article-title":"Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis","volume":"12","author":"Shimada","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/s41589-018-0031-6","article-title":"FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation","volume":"14","author":"Gaschler","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"101250","DOI":"10.1016\/j.drup.2025.101250","article-title":"Targeting SLC7A11 with sorafenib sensitizes stereotactic body radiotherapy in colorectal cancer liver metastasis","volume":"81","author":"He","year":"2025","journal-title":"Drug Resist. Updat."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Kerkhove, L., Geirnaert, F., Rifi, A.L., Law, K.L., Guti\u00e9rrez, A., Oudaert, I., Corbet, C., Gevaert, T., Dufait, I., and De Ridder, M. (2023). Repurposing Sulfasalazine as a Radiosensitizer in Hypoxic Human Colorectal Cancer. Cancers, 15.","DOI":"10.3390\/cancers15082363"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"215919","DOI":"10.1016\/j.canlet.2022.215919","article-title":"PARPi treatment enhances radiotherapy-induced ferroptosis and antitumor immune responses via the cGAS signaling pathway in colorectal cancer","volume":"550","author":"Shen","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/etm.2022.11321","article-title":"Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway","volume":"23","author":"Liu","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4143\/crt.2016.572","article-title":"Ferroptosis: A Novel Anti-tumor Action for Cisplatin","volume":"50","author":"Guo","year":"2018","journal-title":"Cancer Res. Treat."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"288","DOI":"10.5152\/tjg.2023.23300","article-title":"RAS-Selective Lethal 3-Induced Ferroptosis Promotes the Antitumor Efficiency of Anti-Programmed Cell Death Protein 1 Treatment in Colorectal Cancer","volume":"35","author":"Lu","year":"2024","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.1007\/s12013-024-01463-x","article-title":"Iron Overloading Potentiates the Antitumor Activity of 5-Fluorouracil by Promoting Apoptosis and Ferroptosis in Colorectal Cancer Cells","volume":"82","author":"Rah","year":"2024","journal-title":"Cell Biochem. Biophys."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"118014","DOI":"10.1016\/j.biopha.2025.118014","article-title":"Combination therapy with immune checkpoint inhibitors in colorectal cancer: Challenges, resistance mechanisms, and the role of microbiota","volume":"186","author":"Rahimi","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1084\/jem.20180139","article-title":"The cGAS\u2013cGAMP\u2013STING pathway connects DNA damage to inflammation, senescence, and cancer","volume":"215","author":"Li","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-025-03544-y","article-title":"The cGAS-STING pathway in colorectal cancer: Bridging innate immunity and therapeutic strategies","volume":"44","author":"Li","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1158\/2159-8290.CD-14-0863","article-title":"The Vigorous Immune Microenvironment of Microsatellite Instable Colon Cancer Is Balanced by Multiple Counter-Inhibitory Checkpoints","volume":"5","author":"Llosa","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"100824","DOI":"10.1016\/j.jlr.2025.100824","article-title":"Stearoyl-CoA desaturase 1 deficiency drives saturated lipid accumulation and increases liver and plasma acylcarnitines","volume":"66","author":"Kalyesubula","year":"2025","journal-title":"J. Lipid Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4196\/kjpp.2024.28.3.183","article-title":"Ferroptosis and its role in gastric and colorectal cancers","volume":"28","author":"Hou","year":"2024","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Guo, J., Wang, Z., Zhang, Y., Xie, C., Chen, Y., Ma, L., Guo, Z., and Zhang, C. (2026). The dual roles of ferroptosis in digestive tract tumors: Mechanisms, microenvironment regulation, and therapeutic integration with emphasis on immune interactions. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1737847"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature24297","article-title":"Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition","volume":"551","author":"Hangauer","year":"2017","journal-title":"Nature"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.4049\/jimmunol.1302801","article-title":"Oxidized Lipids Block Antigen Cross-Presentation by Dendritic Cells in Cancer","volume":"192","author":"Cao","year":"2014","journal-title":"J. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"532","DOI":"10.18632\/oncotarget.28750","article-title":"Hypoxia induced lipid droplet accumulation promotes resistance to ferroptosis in prostate cancer","volume":"16","author":"Chauhan","year":"2025","journal-title":"Oncotarget"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.4110\/in.2025.25.e6","article-title":"Regulation of Ferroptosis in Cancer and Immune Cells","volume":"25","author":"Jang","year":"2025","journal-title":"Immune Netw."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1016\/j.apsb.2025.09.043","article-title":"Ferroptosis meets cancer immunotherapy: Overcoming the crosstalk challenges through advanced drug delivery strategies","volume":"15","author":"Gan","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cbi.2017.10.011","article-title":"Chemoprevention by artesunate in a preclinical model of colorectal cancer involves down regulation of \u03b2-catenin, suppression of angiogenesis, cellular proliferation and induction of apoptosis","volume":"278","author":"Verma","year":"2017","journal-title":"Chem. Interact."},{"key":"ref_123","unstructured":"El-Ghoneimy, R.A. (2026, March 17). Clinical Study Evaluating the Efficacy and Safety of Sulfasalazine in Patients With Metastatic Colorectal Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06134388."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"107706","DOI":"10.1016\/j.pharmthera.2020.107706","article-title":"Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing","volume":"216","author":"Augustin","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_125","unstructured":"Metanoic Health Ltd. (2026, March 17). Phase II Randomised, Double Blind, Placebo Controlled Trial of Neoadjuvant Artesunate in Stage II\/III Colorectal Cancer, Available online: https:\/\/cdn.clinicaltrials.gov\/large-docs\/09\/NCT07095309\/Prot_000.pdf."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/1471-2407-9-372","article-title":"Early termination of ISRCTN45828668, a phase 1\/2 prospective, randomized study of Sulfasalazine for the treatment of progressing malignant gliomas in adults","volume":"9","author":"Martin","year":"2009","journal-title":"BMC Cancer"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1007\/s10120-017-0720-y","article-title":"Phase 1 study of sulfasalazine and cisplatin for patients with CD44v-positive gastric cancer refractory to cisplatin (EPOC1407)","volume":"20","author":"Shitara","year":"2017","journal-title":"Gastric Cancer"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"19665","DOI":"10.1039\/D5RA03041B","article-title":"Photothermal therapeutic effects and biosafety of a carbon nanoparticles\u2013Fe(ii) complex for triple-negative breast cancer","volume":"15","author":"Huang","year":"2025","journal-title":"RSC Adv."},{"key":"ref_129","unstructured":"(2026, March 17). Sichuan Enray Pharmaceutical Sciences Company Carbon Nanoparticle-Loaded Iron [CNSI-Fe(II)] Dose Escalation Study for the Treatment of Advanced Solid Tumors: Phase 1 Clinical Trial, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06048367."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"vii80","DOI":"10.1093\/neuonc\/noac209.305","article-title":"Ctni-40. Phase I Trial of Sulfasalazine Combined with Stereotactic Radiosurgery for Recurrent Glioblastoma: Study Protocol for NCT04205357","volume":"24","author":"Skeie","year":"2022","journal-title":"Neuro-Oncology"},{"key":"ref_131","unstructured":"Song, L.H. (2026, March 17). Phase II Randomised, Double Blind, Placebo Controlled Trial of Neoadjuvant Artesunate in Stage II\/III Colorectal Cancer in Vietnamese Patients, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03093129."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.cell.2025.12.002","article-title":"Extracellular GPX4 impairs antitumor immunity via dendritic ZP3 receptors","volume":"189","author":"Liu","year":"2026","journal-title":"Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/11\/993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:43:36Z","timestamp":1780544616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/11\/993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":132,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cells15110993"],"URL":"https:\/\/doi.org\/10.3390\/cells15110993","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}