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Wong Education Foundation","award":["82071865"],"award-info":[{"award-number":["82071865"]}]},{"name":"K.C. Wong Education Foundation","award":["81871320"],"award-info":[{"award-number":["81871320"]}]},{"name":"K.C. Wong Education Foundation","award":["32321002"],"award-info":[{"award-number":["32321002"]}]},{"name":"K.C. Wong Education Foundation","award":["82188102"],"award-info":[{"award-number":["82188102"]}]},{"name":"K.C. Wong Education Foundation","award":["92359304"],"award-info":[{"award-number":["92359304"]}]},{"name":"K.C. Wong Education Foundation","award":["2020YFA0804300"],"award-info":[{"award-number":["2020YFA0804300"]}]},{"name":"K.C. Wong Education Foundation","award":["HDMD22H-319373"],"award-info":[{"award-number":["HDMD22H-319373"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed \u201credox reprogramming\u201d. This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms observed in cancer therapy. In this review, we outline the contribution of antioxidant systems to therapeutic resistance. We detail the fundamental constituents of these systems, encompassing the central regulatory mechanisms involving transcription factors (of particular importance is the KEAP1\/NRF2 signaling axis), the molecular effectors of antioxidants, and the auxiliary systems responsible for NADPH generation. Furthermore, we present recent clinical trials based on targeted antioxidant systems for the treatment of cancer, assessing the potential as well as challenges of this strategy in cancer therapy. Additionally, we summarize the pressing issues in the field, with the aim of illuminating a path toward the emergence of novel anticancer therapeutic approaches by orchestrating redox signaling.<\/jats:p>","DOI":"10.3390\/antiox13070778","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T13:26:43Z","timestamp":1719494803000},"page":"778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["The Cancer Antioxidant Regulation System in Therapeutic Resistance"],"prefix":"10.3390","volume":"13","author":[{"given":"Xuanhao","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"},{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"},{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7509-6965","authenticated-orcid":false,"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"},{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"},{"name":"Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, China"},{"name":"The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, China"},{"name":"Zhejiang University Cancer Center, Hangzhou 310003, China"},{"name":"MOE Joint International Research Laboratory of Pancreatic Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"},{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"},{"name":"Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, China"},{"name":"The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, China"},{"name":"Zhejiang University Cancer Center, Hangzhou 310003, China"},{"name":"MOE Joint International Research Laboratory of Pancreatic Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingbo","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"},{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"},{"name":"Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, China"},{"name":"The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, China"},{"name":"Zhejiang University Cancer Center, Hangzhou 310003, China"},{"name":"MOE Joint International Research Laboratory of Pancreatic Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s42255-022-00591-z","article-title":"Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo","volume":"4","author":"Murphy","year":"2022","journal-title":"Nat. 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