{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:13:44Z","timestamp":1792188824192,"version":"4.4.0"},"reference-count":132,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"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>This article reviews pharmacological strategies targeting key metabolic pathways in cancer cells and highlights their inherent limitations, including metabolic plasticity and lack of selectivity. It is proposed that these vulnerabilities can be addressed through a global redox-based approach using high-dose vitamin C. Evidence suggests that the anticancer activity of vitamin C is mediated by its oxidation to dehydroascorbic acid (DHA). Although DHA cannot be administered directly due to its instability, it can be generated in situ within the circulatory system. Once taken up by cancer cells, DHA perturbs multiple redox-sensitive processes, leading to depletion of NADPH and collapse of cellular redox homeostasis. We present a mechanistic framework outlining how controlled generation of DHA may enable a more robust and clinically effective anticancer strategy.<\/jats:p>","DOI":"10.3390\/cells15131212","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:39:11Z","timestamp":1783078751000},"page":"1212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Controlled Generation of Dehydroascorbic Acid: A New Mechanistic Framework for High-Dose Vitamin C Anticancer Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-6043","authenticated-orcid":false,"given":"Alexander V.","family":"Peskin","sequence":"first","affiliation":[{"name":"Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, M\u0101tai H\u0101ora\u2014University of Otago Christchurch, Christchurch 8011, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1158\/0008-5472.CAN-14-3256","article-title":"Redundancy: A critical obstacle to improving cancer therapy","volume":"75","author":"Lavi","year":"2015","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1158\/2159-8290.CD-20-0844","article-title":"Targeting Metabolic Plasticity and Flexibility Dynamics for Cancer Therapy","volume":"10","author":"Fendt","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"216396","DOI":"10.1016\/j.canlet.2023.216396","article-title":"Targeting cancer metabolic pathways for improving chemotherapy and immunotherapy","volume":"575","author":"Luo","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1085\/jgp.8.6.519","article-title":"The metabolism of tumors in the body","volume":"8","author":"Warburg","year":"1927","journal-title":"J. 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