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Copper-mediated novel cell death pathway in tumor cells and implications for innovative cancer therapies

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BIOMEDICINE & PHARMACOTHERAPY
卷 168, 期 -, 页码 -

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ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2023.115730

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Cellular demise modalities; Copper death; Mitochondrial respiration; Tailored therapeutic interventions; Therapeutic strategies; Tumor cell metabolism

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A new mode of cell death, copper death, has been discovered, which is dependent on intracellular copper levels and has a distinct reliance on mitochondrial respiration. Tumor cells with unique metabolic profiles and elevated copper content may be targeted by copper death, making it a potential therapeutic strategy in the field of cancer treatment.
Previous investigations have unraveled an array of cellular demise modalities, encompassing apoptosis, necrosis, pyroptosis, iron death, and several others. These diverse pathways of cell death have been harnessed as therapeutic strategies for eradicating tumor cells. Recent scientific inquiries have unveiled a novel mode of cell death, namely copper death, which is contingent upon intracellular copper levels. Diverging from conventional cell death mechanisms, copper death exhibits a heightened reliance on mitochondrial respiration, specifically the tricarboxylic acid (TCA) cycle. Tumor cells exhibit distinctive metabolic profiles and an elevated copper content compared to their normal counterparts. The emergence of copper death presents a tantalizing prospect for targeted therapies in the realm of cancer treatment. Thus, the primary objective of this review is to introduce the proteins and intricate mechanisms underlying copper death, while comprehensively summarizing the extensive body of knowledge concerning its ramifications across diverse tumor types. The insights garnered from this comprehensive synthesis will serve as an invaluable reference for driving the development of tailor-made therapeutic interventions for tumors.

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