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Such issues are linked to mismatches between oxidative-stress-derived ROS and antioxidant redox efficacy. The review summarizes evidence and recent advances supporting targeting ROS homeostasis and discusses why antioxidant drug effectiveness across tumor suppressors, cell-cycle regulators, and signaling nodes remains uncertain.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/vulnerability-of-antioxidant-drug-therapies-on-targeting-the-nrf2-trp53-jdp2-axis-in-controlling-tumorigenesis/329122/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/vulnerability-of-antioxidant-drug-therapies-on-targeting-the-nrf2-trp53-jdp2-axis-in-controlling-tumorigenesis/329122.png","ImageObject",300,407,{"name":42,"@type":43},"River Wang","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-26","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is oxidative stress and redox balance important in cancer development?","Question",{"text":63,"@type":64},"ROS and redox status regulate oxidative stress and antioxidation pathways that influence proliferation, survival, migration, and metastasis. Disruption of this balance can alter the threshold for cancer cell responses.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What challenges limit antioxidant drug therapies in cancer treatment?",{"text":68,"@type":64},"Antioxidation drugs may lead to tumor resistance or dose-limiting toxicity in host animals and patients. 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Yokoyama 2,3,4, *  \nCitation: Lin, Y.-C.; Ku, C.-C.; Wuputra, K.; Wu, D.-C.; Yokoyama, K.K. Vulnerability of Antioxidant Drug Therapies on Targeting the Nrf2-Trp53-Jdp2 Axis in Controlling Tumorigenesis. Cells 2024, 13, 1648 . [https://doi.org/10.3390/cells13191648](https://doi.org/10.3390/cells13191648)  \nAcademic Editors: Saverio Candido and Alessandro Lavoro  \nReceived: 15 August 2024  \nRevised: 23 September 2024  \nAccepted: 26 September 2024  \nPublished: 3 October 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; [chulin@cc.kmu.edu.tw](chulin@cc.kmu.edu.tw)  \n2 Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; [r991046@gap.kmu.edu.tw](r991046@gap.kmu.edu.tw) (C.-C.K.); [kenlywu@hotmail.com](kenlywu@hotmail.com) (K.W.)  \n3 Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan  \n4 Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan  \n5 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan  \n* Correspondence: [dechwu@yahoo.com](dechwu@yahoo.com) (D.-C.W.); [kazu@kmu.edu.tw](kazu@kmu.edu.tw) (K.K.Y.); Tel.: +886-7312-1001 (ext. 2729) (K.K.Y.); Fax: +886-7313-3849 (K.K.Y.)  \nAbstract: Control of oxidation/antioxidation homeostasis is important for cellular protective functions, and disruption of the antioxidation balance by exogenous and endogenous ligands can lead to profound pathological consequences of cancerous commitment within cells. Although cancers are sensitive to antioxidation drugs, these drugs are sometimes associated with problems including tumor resistance or dose-limiting toxicity in host animals and patients. These problems are often caused by the imbalance between the levels of oxidative stress-induced reactive oxygen species (ROS) and the redox efficacy of antioxidants. Increased ROS levels, because of abnormal function, including metabolic abnormality and signaling aberrations, can promote tumorigenesis and the progression of malignancy, which are generated by genome mutations and activation of proto-oncogene signaling. This hypothesis is supported by various experiments showing that the balance of oxidative stress and redox control is important for cancer therapy. Although many antioxidant drugs exhibit therapeutic potential, there is a heterogeneity of antioxidation functions, including cell growth, cell survival, invasion abilities, and tumor formation, as well as the expression of marker genes including tumor suppressor proteins, cell cycle regulators, nuclear factor erythroid 2-related factor 2, and Jun dimerization protein 2; their effectiveness in cancer remains unproven. Here, we summarize the rationale for the use of antioxidative drugs in preclinical and clinical antioxidant therapy of cancer, and recent advances in this area using cancer cells and their organoids, including the targeting of ROS homeostasis.  \nKeywords: antioxidation; heterogeneity; reactive oxygen species; redox homeostasis; cancer therapy; tumor suppressor p53  \n1. Introduction  \nIt is known that the control of balance between reactive oxygen species (ROS) and redox status is an important way to address the occurrence and development of tumor cells without compromising normal cells [1] . This idea depe","cbCaioTGil6lkTst","https://ap.wps.com/l/cbCaioTGil6lkTst","pdf",1497944,23,"English","# Introduction\n## Oxidation–antioxidation balance and ROS regulation\n## Role of transcription factors (AHR and NRF2)\n## Cancer redox switching and therapeutic implications","[{\"question\":\"Why is oxidative stress and redox balance important in cancer development?\",\"answer\":\"ROS and redox status regulate oxidative stress and antioxidation pathways that influence proliferation, survival, migration, and metastasis. Disruption of this balance can alter the threshold for cancer cell responses.\"},{\"question\":\"What challenges limit antioxidant drug therapies in cancer treatment?\",\"answer\":\"Antioxidation drugs may lead to tumor resistance or dose-limiting toxicity in host animals and patients. These problems are associated with imbalance between ROS levels and antioxidant redox efficacy.\"},{\"question\":\"Which molecular factors are highlighted as key regulators of redox homeostasis?\",\"answer\":\"The review emphasizes transcription factors including AHR and NRF2, as well as marker genes such as tumor suppressor proteins, cell-cycle regulators, and Jun dimerization protein 2.\"}]","Vulnerability of Antioxidant Drug Therapies on Targeting the Nrf2-Trp53-Jdp2 Axis in Controlling Tumorigenesis | PDF",1789982635,58]