{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:44:03Z","timestamp":1783035843743,"version":"3.54.6"},"reference-count":162,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) is a major global health burden characterized by progressive genetic and metabolic alterations, with iron metabolism being increasingly recognized as a key contributor to tumorigenesis. This review provides an integrated synthesis of current evidence on iron metabolism across the continuum of colorectal cancer development, from preneoplastic lesions to advanced disease. We analyzed data from epidemiological, experimental, and mechanistic studies addressing systemic and cellular iron homeostasis, including the hepcidin\u2013ferroportin axis, as well as iron handling within tumor cells and the tumor microenvironment. Available data indicate that colorectal epithelial cells progressively develop an iron-retentive phenotype, characterized by increased iron uptake and reduced export, leading to expansion of the intracellular labile iron pool. This imbalance contributes to oxidative stress, DNA damage, metabolic adaptation, and activation of oncogenic signaling pathways while also influencing immune responses. However, epidemiological findings on dietary iron and CRC risk remain inconsistent, highlighting the context-dependent nature of iron-related effects. In conclusion, iron metabolism represents a dynamic regulator of CRC progression and a mechanistic framework for understanding stage-specific tumor evolution, although further studies are needed to clarify how iron-dependent pathways differ across colorectal tumor subtypes and microenvironmental contexts.<\/jats:p>","DOI":"10.3390\/ijms27125318","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T09:49:51Z","timestamp":1781257791000},"page":"5318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Iron Metabolism in the Colorectal Tumor Microenvironment: From Preneoplastic Lesions to Cancer Progression"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1926-6456","authenticated-orcid":false,"given":"Anamaria-Vl\u0103du\u021ba","family":"Tomoiag\u0103","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, 4th Medical 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(2024). The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094997"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hossain, M.S., Karuniawati, H., Jairoun, A.A., Urbi, Z., Ooi, D.J., John, A., Lim, Y.C., Kibria, K.M.K., Mohiuddin, A.K.M., and Ming, L.C. (2022). Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies. Cancers, 14.","DOI":"10.3390\/cancers14071732"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Malki, A., ElRuz, R.A., Gupta, I., Allouch, A., Vranic, S., and Al Moustafa, A.-E. (2020). Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010130"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.celrep.2015.12.065","article-title":"NCOA4 Deficiency Impairs Systemic Iron Homeostasis","volume":"14","author":"Bellelli","year":"2016","journal-title":"Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1158\/2159-8290.CD-22-0043","article-title":"NCOA4-Mediated Ferritinophagy Is a Pancreatic Cancer Dependency via Maintenance of Iron Bioavailability for Iron\u2013Sulfur Cluster Proteins","volume":"12","author":"Kapner","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nicolini, A., and Ferrari, P. (2024). Involvement of Tumor Immune Microenvironment Metabolic Reprogramming in Colorectal Cancer Progression, Immune Escape, and Response to Immunotherapy. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1353787"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e71185","DOI":"10.1002\/cam4.71185","article-title":"Glucose Metabolic Reprogramming in Colorectal Cancer: From Mechanisms to Targeted Therapy Approaches","volume":"14","author":"Zhou","year":"2025","journal-title":"Cancer Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hu, S., Heng, H., Yang, F., Wang, M., Liu, G., Xiang, Y., and Miao, H. (2025). The Metabolism-Immune Axis in Colorectal Cancer: Remodeling the Tumor Microenvironment through Metabolite Signaling. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1735873"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hon, K.W., Zainal Abidin, S.A., Othman, I., and Naidu, R. (2021). The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.768861"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E7697","DOI":"10.1073\/pnas.1710366114","article-title":"Global Metabolic Reprogramming of Colorectal Cancer Occurs at Adenoma Stage and Is Induced by MYC","volume":"114","author":"Satoh","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"166846","DOI":"10.1016\/j.bbadis.2023.166846","article-title":"Iron Promotes Glycolysis to Drive Colon Tumorigenesis","volume":"1869","author":"Liu","year":"2023","journal-title":"Biochim. Et Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Huang, L., Li, W., Lu, Y., Ju, Q., and Ouyang, M. (2023). Iron Metabolism in Colorectal Cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1098501"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.cmet.2016.07.015","article-title":"Iron Uptake via DMT1 Integrates Cell Cycle with JAK-STAT3 Signaling to Promote Colorectal Tumorigenesis","volume":"24","author":"Xue","year":"2016","journal-title":"Cell Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"114867","DOI":"10.1016\/j.yexcr.2025.114867","article-title":"Metabolic Adaptation in Colorectal Cancer Microenvironment: Focus on Cancer-Associated Fibroblasts (CAFs) and Tumor-Associated Macrophages (TAMs)","volume":"455","author":"Hsu","year":"2026","journal-title":"Exp. Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ahmadi, N., Vidanapathirana, G., and Gopalan, V. (2025). Crossroads of Iron Metabolism and Inflammation in Colorectal Carcinogenesis: Molecular Mechanisms and Therapeutic Perspectives. Genes, 16.","DOI":"10.3390\/genes16101166"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e70168","DOI":"10.1111\/eci.70168","article-title":"Iron-related Intercellular Communication in the Liver: Main Players and Mechanisms","volume":"56","author":"Fonseca","year":"2026","journal-title":"Eur. J. Clin. Invest."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S2468-1253(19)30294-8","article-title":"Modifiable Pathways for Colorectal Cancer: A Mendelian Randomisation Analysis","volume":"5","author":"Cornish","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e71019","DOI":"10.1002\/cam4.71019","article-title":"The Role of Iron Chelation Therapy in Colorectal Cancer: A Systematic Review on Its Mechanisms and Therapeutic Potential","volume":"14","author":"Vidanapathirana","year":"2025","journal-title":"Cancer Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/ejh.14229","article-title":"Serum Ferritin and Risk of Colonic Neoplasia: Implications for the Workup and Treatment of Iron Deficiency","volume":"113","author":"Urback","year":"2024","journal-title":"Eur. J. Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Polizzi, A. (2026). Recent Advances in Research on Iron Metabolism, Ferritin, and Hepcidin. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020906"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/bs.vh.2019.01.002","article-title":"Hepcidin-Ferroportin Axis in Health and Disease","volume":"Volume 110","author":"Ginzburg","year":"2019","journal-title":"Vitamins and Hormones"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Enko, D. (2025). Physiology of Iron Metabolism. Clin. Lab., 71.","DOI":"10.7754\/Clin.Lab.2024.241005"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7373498","DOI":"10.1155\/2020\/7373498","article-title":"A Review of Nutrients and Compounds, Which Promote or Inhibit Intestinal Iron Absorption: Making a Platform for Dietary Measures That Can Reduce Iron Uptake in Patients with Genetic Haemochromatosis","volume":"2020","author":"Milman","year":"2020","journal-title":"J. Nutr. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cronin, S.J.F., Woolf, C.J., Weiss, G., and Penninger, J.M. (2019). The Role of Iron Regulation in Immunometabolism and Immune-Related Disease. Front. Mol. Biosci., 6.","DOI":"10.3389\/fmolb.2019.00116"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1016\/j.celrep.2020.02.049","article-title":"Transferrin Receptor Is a Specific Ferroptosis Marker","volume":"30","author":"Feng","year":"2020","journal-title":"Cell Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev-med-043021-032816","article-title":"Hepcidin and Iron in Health and Disease","volume":"74","author":"Nemeth","year":"2023","journal-title":"Annu. Rev. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nemeth, E., and Ganz, T. (2021). Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126493"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-031-92033-2_3","article-title":"Systemic Iron Metabolism","volume":"1480","author":"Ganz","year":"2025","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3945\/an.116.013961","article-title":"Regulation of the Iron Homeostatic Hormone Hepcidin","volume":"8","author":"Sangkhae","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0140-6736(20)32594-0","article-title":"Iron Deficiency","volume":"397","author":"Pasricha","year":"2021","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1182\/blood-2018-06-815894","article-title":"Liver Iron Sensing and Body Iron Homeostasis","volume":"133","author":"Wang","year":"2019","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1158\/1940-6207.CAPR-10-0113","article-title":"Heme Iron from Meat and Risk of Colorectal Cancer: A Meta-Analysis and a Review of the Mechanisms Involved","volume":"4","author":"Bastide","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chaplin, A., Rodriguez, R.M., Segura-Sampedro, J.J., Ochogav\u00eda-Segu\u00ed, A., Romaguera, D., and Barcel\u00f3-Coblijn, G. (2022). Insights behind the Relationship between Colorectal Cancer and Obesity: Is Visceral Adipose Tissue the Missing Link?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113128"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.3390\/nu5072333","article-title":"Intestinal Iron Homeostasis and Colon Tumorigenesis","volume":"5","author":"Xue","year":"2013","journal-title":"Nutrients"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/CEJ.0b013e32836056f8","article-title":"Association of Dietary and Supplemental Iron and Colorectal Cancer in a Population-Based Study","volume":"22","author":"Ashmore","year":"2013","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1007\/s13402-023-00828-3","article-title":"Iron Metabolism in Colorectal Cancer: A Balancing Act","volume":"46","author":"Cardoso","year":"2023","journal-title":"Cell. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yousefi, M.H., Masoudi, A., Saberi Rounkian, M., Mansouri, M., Hojat, B., Kaveh Samani, M., Veisi, R., Honarvar Bakeshloo, P., Nosratipour, R., and Afkhami, H. (2025). An Overview of the Current Evidences on the Role of Iron in Colorectal Cancer: A Review. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1499094"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Aksan, A., Farrag, K., Aksan, S., Schroeder, O., and Stein, J. (2021). Flipside of the Coin: Iron Deficiency and Colorectal Cancer. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.635899"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zeidan, R.S., Yoon, H.-S., Yang, J.J., Sobh, A., Braithwaite, D., Mankowski, R., Leeuwenburgh, C., and Anton, S. (2024). Iron and Cancer: Overview of the Evidence from Population-Based Studies. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1393195"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1080\/10408398.2021.1982861","article-title":"Iron Intake and Multiple Health Outcomes: Umbrella Review","volume":"63","author":"Huang","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1158\/1055-9965.EPI-13-0733","article-title":"Iron and Cancer Risk\u2014A Systematic Review and Meta-Analysis of the Epidemiological Evidence","volume":"23","author":"Jakszyn","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_43","first-page":"1529","article-title":"Dietary Intake of Total, Heme and Non-Heme Iron and the Risk of Colorectal Cancer in a European Prospective Cohort Study","volume":"128","author":"Aglago","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/ijc.2910560315","article-title":"Body Iron Stores and Risk of Cancer","volume":"56","author":"Knekt","year":"1994","journal-title":"Int. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sch\u00f6ttker, B., G\u00e0o, X., Jansen, E.H.J.M., and Brenner, H. (2021). Associations of Human Colorectal Adenoma with Serum Biomarkers of Body Iron Stores, Inflammation and Antioxidant Protein Thiols. Antioxidants, 10.","DOI":"10.3390\/antiox10081195"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/jnci\/djh047","article-title":"Heme Iron, Zinc, Alcohol Consumption, and Colon Cancer: Iowa Women\u2019s Health Study","volume":"96","author":"Lee","year":"2004","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1111\/jcmm.12764","article-title":"The Risk of New-Onset Cancer Associated with HFE C282Y and H63D Mutations: Evidence from 87,028 Participants","volume":"20","author":"Lv","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1002\/hep.23448","article-title":"HFE C282Y Homozygotes Are at Increased Risk of Breast and Colorectal Cancer\u2020","volume":"51","author":"Osborne","year":"2010","journal-title":"Hepatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1007\/s00204-021-03064-6","article-title":"Chronic Intestinal Inflammation Drives Colorectal Tumor Formation Triggered by Dietary Heme Iron in Vivo","volume":"95","author":"Seiwert","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41579-024-01090-6","article-title":"Bacterial Siderophores: Diversity, Uptake Pathways and Applications","volume":"23","author":"Schalk","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2221978","DOI":"10.1080\/19490976.2023.2221978","article-title":"Dietary Iron Modulates Gut Microbiota and Induces SLPI Secretion to Promote Colorectal Tumorigenesis","volume":"15","author":"Liu","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Singh, V., Lee, G., Son, H., Koh, H., Kim, E.S., Unno, T., and Shin, J.-H. (2023). Butyrate Producers, \u201cThe Sentinel of Gut\u201d: Their Intestinal Significance with and beyond Butyrate, and Prospective Use as Microbial Therapeutics. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1103836"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1093\/nutrit\/nuaa040","article-title":"Iron Deficiency, Immunology, and Colorectal Cancer","volume":"79","author":"Phipps","year":"2021","journal-title":"Nutr. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Rebersek, M. (2021). Gut Microbiome and Its Role in Colorectal Cancer. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-09054-2"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Liu, Y., He, W., Yang, J., He, Y., Wang, Z., and Li, K. (2021). The Effects of Preoperative Intestinal Dysbacteriosis on Postoperative Recovery in Colorectal Cancer Surgery: A Prospective Cohort Study. BMC Gastroenterol., 21.","DOI":"10.1186\/s12876-021-02035-6"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1726309","DOI":"10.1155\/2020\/1726309","article-title":"Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition","volume":"2020","author":"Aceto","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1136\/gut.2006.094060","article-title":"Modulation of Iron Transport Proteins in Human Colorectal Carcinogenesis","volume":"55","author":"Brookes","year":"2006","journal-title":"Gut"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/mutage\/geq028","article-title":"Oxidative Stress and 8-Oxoguanine Repair Are Enhanced in Colon Adenoma and Carcinoma Patients","volume":"25","author":"Obtulowicz","year":"2010","journal-title":"Mutagenesis"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.freeradbiomed.2017.01.017","article-title":"HNE and Cholesterol Oxidation Products in Colorectal Inflammation and Carcinogenesis","volume":"111","author":"Rossin","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1158\/1940-6207.CAPR-11-0103","article-title":"Iron Homeostasis and Distal Colorectal Adenoma Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial","volume":"4","author":"Cross","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1093\/jnci\/dji165","article-title":"Hemochromatosis Gene Mutations, Body Iron Stores, Dietary Iron, and Risk of Colorectal Adenoma in Women","volume":"97","author":"Chan","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yuan, Y., Ni, S., Zhuge, A., Li, B., and Li, L. (2021). Iron Regulates the Warburg Effect and Ferroptosis in Colorectal Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.614778"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1158\/2159-8290.CD-23-1379","article-title":"Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers","volume":"14","author":"Shanmugam","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Wang, J.-D., Xu, G.-S., Hu, X.-L., Li, W.-Q., Yao, N., Han, F.-Z., Zhang, Y., and Qu, J. (2024). The Histologic Features, Molecular Features, Detection and Management of Serrated Polyps: A Review. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1356250"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1158\/1055-9965.EPI-09-0309","article-title":"Transferrin Dipstick as a Potential Novel Test for Colon Cancer Screening: A Comparative Study with Immuno Fecal Occult Blood Test","volume":"18","author":"Sheng","year":"2009","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00259-025-07493-8","article-title":"Synthesis and Preclinical Evaluation of a 68Ga-Labeled Peptide for PET Imaging of Transferrin Receptor 1 in Tumor","volume":"53","author":"Lin","year":"2025","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"62107","DOI":"10.1021\/acsomega.5c09356","article-title":"Design and Preclinical Evaluation of a 68Ga-Labeled Macrocyclic Peptide PET Probe Targeting Transferrin Receptor 1 in Colorectal Cancer","volume":"10","author":"Zhu","year":"2025","journal-title":"ACS Omega"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3109\/00365529709000200","article-title":"Significance of Serum Iron and Ferritin in Patients with Colorectal Adenomas","volume":"32","author":"Kishida","year":"1997","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1743-7075-11-21","article-title":"Systemic and Tumor Level Iron Regulation in Men with Colorectal Cancer: A Case Control Study","volume":"11","author":"Pusatcioglu","year":"2014","journal-title":"Nutr. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.canlet.2005.07.001","article-title":"Altered Iron Metabolism, Transferrin Receptor 1 and Ferritin in Patients with Colon Cancer","volume":"238","author":"Prutki","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5573","DOI":"10.1007\/s11033-013-2659-3","article-title":"Alterations in Expression Profile of Iron-Related Genes in Colorectal Cancer","volume":"40","author":"Hamara","year":"2013","journal-title":"Mol. Biol. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3892\/ol.2024.14857","article-title":"Role of the Human Cytochrome B561 Family in Iron Metabolism and Tumors (Review)","volume":"29","author":"Zhou","year":"2024","journal-title":"Oncol. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"jcs263402","DOI":"10.1242\/jcs.263402","article-title":"The STEAP4 Target NQO1 Mediates Colon Tumorigenesis","volume":"138","author":"Yin","year":"2025","journal-title":"J. Cell Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"E9608","DOI":"10.1073\/pnas.1712946114","article-title":"Quantitative Proteomics Identifies STEAP4 as a Critical Regulator of Mitochondrial Dysfunction Linking Inflammation and Colon Cancer","volume":"114","author":"Xue","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e143691","DOI":"10.1172\/JCI143691","article-title":"HIF-2\u03b1 Activation Potentiates Oxidative Cell Death in Colorectal Cancers by Increasing Cellular Iron","volume":"131","author":"Singhal","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"109021","DOI":"10.1016\/j.cbi.2020.109021","article-title":"Iron and Hepcidin Mediate Human Colorectal Cancer Cell Growth","volume":"319","author":"Sornjai","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Di Grazia, A., Di Fusco, D., Franz\u00e8, E., Colella, M., Strimpakos, G., Salvatori, S., Formica, V., Laudisi, F., Maresca, C., and Colantoni, A. (2022). Hepcidin Upregulation in Colorectal Cancer Associates with Accumulation of Regulatory Macrophages and Epithelial\u2013Mesenchymal Transition and Correlates with Progression of the Disease. Cancers, 14.","DOI":"10.3390\/cancers14215294"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"39542","DOI":"10.1038\/s41598-025-23180-y","article-title":"NCOA4-Mediated Ferroptosis Conducive to EMT Inhibition in Colorectal Cancer Cells Was Achieved through the PI3K\/AKT\/MTOR Pathway","volume":"15","author":"Fu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1186\/s12964-024-01769-6","article-title":"Inhibition of IRP2-Dependent Reprogramming of Iron Metabolism Suppresses Tumor Growth in Colorectal Cancer","volume":"22","author":"Hwang","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1111\/cas.13234","article-title":"BRAF Mutations Are Associated with Increased Iron Regulatory Protein-2 Expression in Colorectal Tumorigenesis","volume":"108","author":"Horniblow","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1111\/cas.13389","article-title":"Lipocalin 2 Negatively Regulates Cell Proliferation and Epithelial to Mesenchymal Transition through Changing Metabolic Gene Expression in Colorectal Cancer","volume":"108","author":"Kim","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1016\/j.dld.2022.01.131","article-title":"Possible Role of Nuclear Factor Erythroid 2\u2013Related Factor 2 in the Progression of Human Colon Precancerous Lesions","volume":"54","author":"Polimeno","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"16479","DOI":"10.1007\/s00210-025-04324-3","article-title":"NRF2 as a Ferroptosis Gatekeeper in Colorectal Cancer: Implications for Therapy","volume":"398","author":"Alkhathami","year":"2025","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e181032","DOI":"10.1172\/jci.insight.181032","article-title":"Epithelial HO-1 Regulates Iron Availability and Promotes Colonic Tumorigenesis in a Context-Dependent Manner","volume":"11","author":"Callahan","year":"2026","journal-title":"JCI Insight"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/978-3-031-92033-2_18","article-title":"Iron and Cancer","volume":"Volume 1480","author":"Torti","year":"2025","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13062-023-00373-x","article-title":"IGF2BP2 Promotes Colorectal Cancer Progression by Upregulating the Expression of TFRC and Enhancing Iron Metabolism","volume":"18","author":"Liu","year":"2023","journal-title":"Biol. Direct"},{"key":"ref_87","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":"19","author":"Hu","year":"2026","journal-title":"Onco. Targets. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"142797","DOI":"10.1016\/j.ijbiomac.2025.142797","article-title":"STEAP Proteins: Roles in Disease Biology and Potential for Therapeutic Intervention","volume":"309","author":"Cai","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Frascatani, R., Colella, M., and Monteleone, G. (2024). Hepcidin Is a Valuable Therapeutic Target for Colorectal Cancer. Cancers, 16.","DOI":"10.3390\/cancers16234068"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1007\/s12011-022-03488-w","article-title":"M2 Macrophage-Derived Exosomal Ferritin Heavy Chain Promotes Colon Cancer Cell Proliferation","volume":"201","author":"Cui","year":"2023","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_91","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_92","doi-asserted-by":"crossref","first-page":"115188","DOI":"10.1016\/j.intimp.2025.115188","article-title":"Sodium Butyrate Induces Ferroptosis in Colorectal Cancer Cells by Promoting NCOA4-FTH1-Mediated Ferritinophagy","volume":"163","author":"Liu","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Forciniti, S., Greco, L., Grizzi, F., Malesci, A., and Laghi, L. (2020). Iron Metabolism in Cancer Progression. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062257"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3892\/ijmm.2024.5480","article-title":"Iron Metabolism and the Tumor Microenvironment: A New Perspective on Cancer Intervention and Therapy (Review)","volume":"55","author":"Bu","year":"2024","journal-title":"Int. J. Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e15904","DOI":"10.1002\/adma.202515904","article-title":"Antagonistic Iron Competition Induced by Iron Chelators Heightens Cuproptosis in Both Tumors and Intratumoral Bacteria","volume":"38","author":"Xie","year":"2026","journal-title":"Adv. Mater."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"156802","DOI":"10.1172\/jci.insight.156802","article-title":"Iron Accelerates Fusobacterium Nucleatum\u2013Induced CCL8 Expression in Macrophages and Is Associated with Colorectal Cancer Progression","volume":"7","author":"Yamane","year":"2022","journal-title":"JCI Insight"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41556-023-01314-6","article-title":"Gut Microbial Metabolite Facilitates Colorectal Cancer Development via Ferroptosis Inhibition","volume":"26","author":"Cui","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1158\/0008-5472.CAN-24-0275","article-title":"Gut Microbiome Mediates Ferroptosis Resistance for Colorectal Cancer Development","volume":"84","author":"Zhang","year":"2024","journal-title":"Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1002\/ijc.33711","article-title":"Lipocalin 2 Expression Promotes Tumor Progression and Therapy Resistance by Inhibiting Ferroptosis in Colorectal Cancer","volume":"149","author":"Chaudhary","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Chieppa, M., Kashyrina, M., Miraglia, A., and Vardanyan, D. (2024). Enhanced CRC Growth in Iron-Rich Environment, Facts and Speculations. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212389"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/cge.12968","article-title":"Erythropoietic Protoporphyria a Clinical and Molecular Study from Lebanon: Ferrochelatase a Potential Tumor Suppressor Gene in Colon Cancer","volume":"92","author":"Kadara","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1096\/fj.07-8888com","article-title":"Silencing of Human Ferrochelatase Causes Abundant Protoporphyrin-IX Accumulation in Colon Cancer","volume":"22","author":"Kemmner","year":"2008","journal-title":"FASEB J."},{"key":"ref_103","first-page":"991","article-title":"Protoporphyrin IX Occurs Naturally in Colorectal Cancers and Their Metastases","volume":"61","author":"Moesta","year":"2001","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Jain, C., Essani, M., Kumar, R., Das, N.K., Singhal, R., Rossiter, N.J., Chen, B., Huang, W., Lee, Z.H., and Solanki, S. (Cell Metab., 2026). Iron-Addicted Colorectal Cancers Exploit Heme-Complex II Axis to Resist Oxidative Cell Death, Cell Metab., in press.","DOI":"10.1016\/j.cmet.2026.04.020"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"108661","DOI":"10.1016\/j.abb.2020.108661","article-title":"Evolution of the Human Mitochondrial ABCB7 [2Fe\u20132S](GS)4 Cluster Exporter and the Molecular Mechanism of an E433K Disease-Causing Mutation","volume":"697","author":"Pearson","year":"2021","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"119733","DOI":"10.1016\/j.bbamcr.2024.119733","article-title":"Mitochondria Function in Cytoplasmic FeS Protein Biogenesis","volume":"1871","author":"Dancis","year":"2024","journal-title":"Biochim. Et Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1038\/s41467-022-32006-8","article-title":"Structures of Atm1 Provide Insight into [2Fe-2S] Cluster Export from Mitochondria","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/s41594-020-0454-0","article-title":"Structural Insights into Fe\u2013S Protein Biogenesis by the CIA Targeting Complex","volume":"27","author":"Kassube","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-biochem-013118-110644","article-title":"Redox Chemistry in the Genome: Emergence of the [4Fe4S] Cofactor in Repair and Replication","volume":"88","author":"Barton","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.7150\/jca.19364","article-title":"Downregulation of ABC Transporters in Non-Neoplastic Tissues Confers Better Prognosis for Pancreatic and Colorectal Cancer Patients","volume":"8","author":"Dvorak","year":"2017","journal-title":"J. Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/mutage\/ger075","article-title":"The Role of ABC Transporters in Progression and Clinical Outcome of Colorectal Cancer","volume":"27","author":"Hlavata","year":"2012","journal-title":"Mutagenesis"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7449941","DOI":"10.1155\/2022\/7449941","article-title":"Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"16497","DOI":"10.1038\/srep16497","article-title":"Regulation of Iron Homeostasis by the P53-ISCU Pathway","volume":"5","author":"Funauchi","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Petronek, M.S., and Allen, B.G. (2023). Maintenance of Genome Integrity by the Late-Acting Cytoplasmic Iron-Sulfur Assembly (CIA) Complex. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1152398"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1126\/science.1219723","article-title":"MMS19 Assembles Iron-Sulfur Proteins Required for DNA Metabolism and Genomic Integrity","volume":"337","author":"Stehling","year":"2012","journal-title":"Science"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.molcel.2017.11.010","article-title":"Cytosolic Iron-Sulfur Assembly Is Evolutionarily Tuned by a Cancer-Amplified Ubiquitin Ligase","volume":"69","author":"Weon","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Hashimoto, E., Ohuchi, M., Nomura, M., Miyahara, S., Hayashi, K., Saito, M., Yamashita, Y., Shimada, M., Yamada, H., and Tanuma, N. (2026). The Iron-Sulfur Cluster Assembly Factor FDX2 Is Required for Tumor Initiation but Not for Growth of Established Tumors in Transplantation Models. J. Biol. Chem., 113200.","DOI":"10.1016\/j.jbc.2026.113200"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"E39","DOI":"10.1161\/RES.0000000000000110","article-title":"Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System","volume":"119","author":"Griendling","year":"2016","journal-title":"Circ. Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Zi\u0144czuk, J., Maciejczyk, M., Zar\u0119ba, K., Pryczynicz, A., Dymicka-Piekarska, V., Kami\u0144ska, J., Koper-Lenkiewicz, O., Matowicka-Karna, J., K\u0119dra, B., and Zalewska, A. (2020). Pro-Oxidant Enzymes, Redox Balance and Oxidative Damage to Proteins, Lipids and DNA in Colorectal Cancer Tissue. Is Oxidative Stress Dependent on Tumour Budding and Inflammatory Infiltration?. Cancers, 12.","DOI":"10.3390\/cancers12061636"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"60343","DOI":"10.1007\/s11356-023-26702-1","article-title":"Lipid Peroxidation Mediates the Association between Iron Overload and Liver Injury: Cross-Sectional and Longitudinal Analyses in General Chinese Urban Adults","volume":"30","author":"Wang","year":"2023","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1158\/0008-5472.CAN-14-2554","article-title":"A Central Role for Heme Iron in Colon Carcinogenesis Associated with Red Meat Intake","volume":"75","author":"Bastide","year":"2015","journal-title":"Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1093\/carcin\/bgw035","article-title":"Red Meat and Colorectal Cancer: Nrf2-Dependent Antioxidant Response Contributes to the Resistance of Preneoplastic Colon Cells to Fecal Water of Hemoglobin- and Beef-Fed Rats","volume":"37","author":"Surya","year":"2016","journal-title":"Carcinogenesis"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"103367","DOI":"10.1016\/j.critrevonc.2021.103367","article-title":"Iron Overload-Induced Oxidative Stress in Myelodysplastic Syndromes and Its Cellular Sequelae","volume":"163","author":"Kim","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1080\/10715762.2020.1851027","article-title":"Protein Carbonylation: Molecular Mechanisms, Biological Implications, and Analytical Approaches","volume":"55","author":"Akagawa","year":"2021","journal-title":"Free Radic. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1007\/s12013-025-01827-x","article-title":"Biochemical Insights into Oxidative Stress in Colon Cancer Patients","volume":"83","author":"Sulaiman","year":"2025","journal-title":"Cell Biochem. Biophys."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1089\/ars.2020.8148","article-title":"NRF2 and Hypoxia-Inducible Factors: Key Players in the Redox Control of Systemic Iron Homeostasis","volume":"35","author":"Duarte","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"7866","DOI":"10.1074\/jbc.M116.768283","article-title":"NADPH Oxidase 1 Supports Proliferation of Colon Cancer Cells by Modulating Reactive Oxygen Species-Dependent Signal Transduction","volume":"292","author":"Juhasz","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"38113","DOI":"10.18632\/oncotarget.17494","article-title":"Interleukin-4 and Interleukin-13 Increase NADPH Oxidase 1-Related Proliferation of Human Colon Cancer Cells","volume":"8","author":"Liu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00018-025-05982-5","article-title":"Ferroptosis and Cancer: When Iron Turns against Tumors","volume":"83","author":"Toyokuni","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/or.2026.9143","article-title":"Ferroptosis in Colorectal Cancer: Molecular Mechanisms and Regulatory Crosstalk with Therapeutic Prospects (Review)","volume":"56","author":"Wu","year":"2026","journal-title":"Oncol. Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"105050","DOI":"10.1016\/j.yexmp.2026.105050","article-title":"The Functional Role of Ferroptosis in the Development and Progression of Common Cancers","volume":"146","author":"Ostrowska","year":"2026","journal-title":"Exp. Mol. Pathol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.freeradbiomed.2025.08.051","article-title":"RBMS2 Mediates SLC7A11 Transcription-Translation to Regulate Ferroptosis in Colorectal Cancer","volume":"240","author":"Wang","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"822","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_134","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1038\/s41388-025-03457-2","article-title":"PRMT5 K240lac Confers Ferroptosis Resistance via ALKBH5\/SLC7A11 Axis in Colorectal Cancer","volume":"44","author":"Qu","year":"2025","journal-title":"Oncogene"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e71231","DOI":"10.1096\/fj.202502018R","article-title":"LEF1 Suppresses Ferroptosis in Colorectal Cancer Cells by Targeted Promotion of SLC7A11 Transcription","volume":"39","author":"Chen","year":"2025","journal-title":"FASEB J."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1200\/JCO.2025.43.4_suppl.211","article-title":"Sensitizing K-Ras G12D Mutant Colorectal Patient-Derived Organoids via Ferroptosis Pathway","volume":"43","author":"De","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"117769","DOI":"10.1016\/j.bcp.2026.117769","article-title":"Iron Homeostasis and Ferroptosis: A Converging Axis in Cancer Therapy","volume":"249","author":"Sajeev","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4734","DOI":"10.1158\/0008-5472.CAN-24-4949","article-title":"CLK2 Regulates the KEAP1\/NRF2 and P53 Pathways to Suppress Ferroptosis in Colorectal Cancer","volume":"85","author":"Zhou","year":"2025","journal-title":"Cancer Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.molcel.2021.12.001","article-title":"Persister Cancer Cells: Iron Addiction and Vulnerability to Ferroptosis","volume":"82","author":"Rodriguez","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Mahemuti, D., Ma, L., Siddiqe, W., Tang, Z., Kong, Y., Li, W., Zhang, Z., Su, Z., and Maimaitijiang, A. (2026). Ferroptosis as a Novel Therapeutic Strategy to Overcome Multidrug Resistance in Colorectal Cancer. Pharmaceuticals, 19.","DOI":"10.3390\/ph19020252"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"14359","DOI":"10.1038\/s41598-023-41490-x","article-title":"Nrf2 Inhibition Increases Sensitivity to Chemotherapy of Colorectal Cancer by Promoting Ferroptosis and Pyroptosis","volume":"13","author":"Huang","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1007\/s11033-026-11690-5","article-title":"Repression of FOSL1 Augments Ferroptosis to Overcome Oxaliplatin Resistance in Colorectal Cancer by Acting on SRSF2","volume":"53","author":"Zhu","year":"2026","journal-title":"Mol. Biol. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"37189","DOI":"10.1038\/s41598-025-14086-w","article-title":"Targeting FBXL5 to Induce Ferroptosis and Reverse Oxaliplatin Resistance in Iron-Rich Colorectal Cancer","volume":"15","author":"Wang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Xia, W., Lv, Y., Zou, Y., Kang, Z., Li, Z., Tian, J., Zhou, H., Su, W., and Zhong, J. (2025). The Role of Ferroptosis in Colorectal Cancer and Its Potential Synergy with Immunotherapy. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1526749"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Piccolo, M., Ferraro, M.G., Iazzetti, F., Santamaria, R., and Irace, C. (2024). Insight into Iron, Oxidative Stress and Ferroptosis: Therapy Targets for Approaching Anticancer Strategies. Cancers, 16.","DOI":"10.3390\/cancers16061220"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s10495-026-02377-0","article-title":"Metabolic Regulation of Ferroptosis in Cancer: Mechanisms, Pharmacological Inducers, and Translational Challenges","volume":"31","author":"Liu","year":"2026","journal-title":"Apoptosis"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/s41418-022-00998-x","article-title":"Non-Coding RNAs and Ferroptosis: Potential Implications for Cancer Therapy","volume":"29","author":"Balihodzic","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"109061","DOI":"10.1016\/j.bioorg.2025.109061","article-title":"Structure\u2013Activity Optimization of Deferasirox\u2013Derived Aroyl Hydrazones: Synthesis, DFT Characterization, and Mechanistic Insights into Selective Anticancer Activity against Colon and Breast Cancer","volume":"165","author":"Dilek","year":"2025","journal-title":"Bioorg. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Trabolsi, A., Lekakis, M., Commisso, P.M., Gandhi, N., Elliott, A., Liu, S.V., Ma, P.C., Hoon, D.S.B., Wei, S., and Antonarakis, E.S. (2026). Transferrin Receptor Overexpression in Solid Tumors Is Associated with Inflamed Microenvironments and Upregulated Immune Checkpoints, with Implications for Immunotherapy Sensitivity. Cancers, 18.","DOI":"10.3390\/cancers18091402"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/978-3-031-92033-2_26","article-title":"Current Landscape of Hepcidin Therapeutics","volume":"1480","author":"Nai","year":"2025","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/bs.vh.2024.10.003","article-title":"Hepcidin: A Multifaceted Hormone in Iron Homeostasis and Tumor Biology","volume":"129","author":"Liu","year":"2025","journal-title":"Vitam. Horm."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/s41416-023-02149-6","article-title":"Ferroptosis in Colorectal Cancer: A Future Target?","volume":"128","author":"Yan","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"66475","DOI":"10.1021\/acsami.5c19528","article-title":"Self-Assembly Albumin Nanoparticles for Improved Anticancer Effect and Reinforced Ferroptosis in Metastatic Colorectal Cancer Treatment","volume":"17","author":"Xu","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41392-025-02296-7","article-title":"Acevaltrate as a Novel Ferroptosis Inducer with Dual Targets of PCBP1\/2 and GPX4 in Colorectal Cancer","volume":"10","author":"Yu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"104151","DOI":"10.1016\/j.redox.2026.104151","article-title":"Targeting HIF-1\u03b1 Promotes Ferroptosis and Boosts Antitumor Immunity in MSS Colorectal Cancer","volume":"93","author":"Yang","year":"2026","journal-title":"Redox Biol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Formica, V., Di Grazia, A., Bonomo, M.V., Frascatani, R., Mancone, R., and Monteleone, G. (2024). Circulating Hepcidin Levels Are an Independent Predictor of Survival in Microsatellite Stable Metastatic Colorectal Cancer Patient Candidates for Standard First-Line Treatment. Cancers, 16.","DOI":"10.3390\/cancers16233977"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1186\/s12967-025-07018-9","article-title":"Impact of Iron Deficiency on Therapeutic Outcomes in Colorectal Cancer Patients: A Single-Center Cohort Study","volume":"23","author":"Luo","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Erichsen, C., Rosberg, V., and Krarup, P.-M. (2024). Streamlined Preoperative Iron Deficiency Screening and IV Treatment for Colorectal Cancer Patients beyond Clinical Trials. J. Clin. Med., 13.","DOI":"10.3390\/jcm13196002"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1002\/cam4.4956","article-title":"Low Ferroptosis Score Predicts Chemotherapy Responsiveness and Immune-activation in Colorectal Cancer","volume":"12","author":"Lv","year":"2023","journal-title":"Cancer Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"109028","DOI":"10.1016\/j.pharmthera.2026.109028","article-title":"Advances in Iron-Based Chemodynamic Anti-Cancer Therapy","volume":"283","author":"Dai","year":"2026","journal-title":"Pharmacol. Ther."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Zhu, J., Zhang, J., Lou, Y., Zheng, Y., Zheng, X., Cen, W., Ye, L., and Zhang, Q. (2024). Developing a Machine Learning-Based Prognosis and Immunotherapeutic Response Signature in Colorectal Cancer: Insights from Ferroptosis, Fatty Acid Dynamics, and the Tumor Microenvironment. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1416443"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e70024","DOI":"10.1002\/biof.70024","article-title":"Targeting Cellular Energetics via Ferroptosis Mediated Cell Death in Resistant Colorectal Cancer Stem Cells","volume":"51","author":"Biswas","year":"2025","journal-title":"BioFactors"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5318\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T09:54:01Z","timestamp":1781258041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":162,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125318"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125318","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]}}}