Controlled Generation of Dehydroascorbic Acid: A New Mechanistic Framework for High-Dose Vitamin C Anticancer Therapy.

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.