Harnessing copper: Innovative approaches to combat neurodegenerative diseases and cancer (Review)

Bost M, Houdart S, Oberli M, Kalonji E, Huneau JF and Margaritis I: Dietary copper and human health: Current evidence and unresolved issues. J Trace Elem Med Biol. 35:107–115. 2016. View Article : Google Scholar : PubMed/NCBI

Huang F, Lu X, Kuai L, Ru Y, Jiang J, Song J, Chen S, Mao L, Li Y, Li B, et al: Dual-Site Biomimetic Cu/Zn-MOF for atopic dermatitis catalytic therapy via suppressing FcүR-mediated phagocytosis. J Am Chem Soc. 146:3186–3199. 2024. View Article : Google Scholar : PubMed/NCBI

Ash D, Sudhahar V, Youn SW, Okur MN, Das A, O'Bryan JP, McMenamin M, Hou Y, Kaplan JH, Fukai T and Ushio-Fukai M: The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2. Nat Commun. 12:30912021. View Article : Google Scholar : PubMed/NCBI

Ding H, Gao YS, Wang Y, Hu C, Sun Y and Zhang C: Dimethyloxaloylglycine increases the bone healing capacity of adipose-derived stem cells by promoting osteogenic differentiation and angiogenic potential. Stem Cells Dev. 23:990–1000. 2014. View Article : Google Scholar :

Akhtar H, Alhamoudi FH, Marshall J, Ashton T, Darr JA, Rehman IU, Chaudhry AA and Reilly G: Synthesis of cerium, zirconium, and copper doped zinc oxide nanoparticles as potential biomaterials for tissue engineering applications. Heliyon. 10:e291502024. View Article : Google Scholar : PubMed/NCBI

Han J, Luo J, Wang C, Kapilevich L and Zhang XA: Roles and mechanisms of copper homeostasis and cuproptosis in osteoarticular diseases. Biomed Pharmacother. 174:1165702024. View Article : Google Scholar : PubMed/NCBI

Wei M, Huang Q, Dai Y, Zhou H, Cui Y, Song W, Di D, Zhang R, Li C, Wang Q and Jing T: Manganese, iron, copper, and selenium co-exposure and osteoporosis risk in Chinese adults. J Trace Elem Med Biol. 72:1269892022. View Article : Google Scholar : PubMed/NCBI

Xiao T, Ackerman CM, Carroll EC, Jia S, Hoagland A, Chan J, Thai B, Liu CS, Isacoff EY and Chang CJ: Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system. Nat Chem Biol. 14:655–663. 2018. View Article : Google Scholar : PubMed/NCBI

Benatar M, Robertson J and Andersen PM: Amyotrophic lateral sclerosis caused by SOD1 variants: From genetic discovery to disease prevention. Lancet Neurol. 24:77–86. 2025. View Article : Google Scholar

Horvath R, Kemp JP, Tuppen HA, Hudson G, Oldfors A, Marie SK, Moslemi AR, Servidei S, Holme E, Shanske S, et al: Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy. Brain. 132(Pt 11): 3165–3174. 2009. View Article : Google Scholar : PubMed/NCBI

Qu Y, Zhan Q, Du S, Ding Y, Fang B, Du W, Wu Q, Yu H, Li L and Huang W: Catalysis-based specific detection and inhibition of tyrosinase and their application. J Pharm Anal. 10:414–425. 2020. View Article : Google Scholar : PubMed/NCBI

Foehr R, Anderson K, Dombrowski O, Foehr A and Foehr ED: Dysregulation of extracellular matrix and lysyl oxidase in Ehlers-Danlos syndrome type IV skin fibroblasts. Orphanet J Rare Dis. 19:92024. View Article : Google Scholar : PubMed/NCBI

Wassenberg T, Deinum J, van Ittersum FJ, Kamsteeg EJ, Pennings M, Verbeek MM, Wevers RA, van Albada ME, Kema IP, Versmissen J, et al: Clinical presentation and long-term follow-up of dopamine beta hydroxylase deficiency. J Inherit Metab Dis. 44:554–565. 2021. View Article : Google Scholar

De Feyter S, Beyens A and Callewaert B: ATP7A-related copper transport disorders: A systematic review and definition of the clinical subtypes. J Inherit Metab Dis. 46:163–173. 2023. View Article : Google Scholar : PubMed/NCBI

Stalke A, Behrendt A, Hennig F, Gohlke H, Buhl N, Reinkens T, Baumann U, Schlegelberger B, Illig T, Pfister ED and Skawran B: Functional characterization of novel or yet uncharacterized ATP7B missense variants detected in patients with clinical Wilson's disease. Clin Genet. 104:174–185. 2023. View Article : Google Scholar : PubMed/NCBI

Li Y, Ma J, Wang R, Luo Y, Zheng S and Wang X: Zinc transporter 1 functions in copper uptake and cuproptosis. Cell Metab. 36:2118–2129 e6. 2024. View Article : Google Scholar : PubMed/NCBI

Ohgami RS, Campagna DR, McDonald A and Fleming MD: The Steap proteins are metalloreductases. Blood. 108:1388–1394. 2006. View Article : Google Scholar : PubMed/NCBI

Wyman S, Simpson RJ, McKie AT and Sharp PA: Dcytb (Cybrd1) functions as both a ferric and a cupric reductase in vitro. FEBS Lett. 582:1901–1906. 2008. View Article : Google Scholar : PubMed/NCBI

Kleven MD, Dlakic M and Lawrence CM: Characterization of a Single b-type Heme, FAD, and metal binding sites in the transmembrane domain of six-transmembrane epithelial antigen of the prostate (STEAP) family proteins. J Biol Chem. 290:22558–22569. 2015. View Article : Google Scholar : PubMed/NCBI

Kirsipuu T, Zadorožnaja A, Smirnova J, Friedemann M, Plitz T, Tõugu V and Palumaa P: Copper(II)-binding equilibria in human blood. Sci Rep. 10:56862020. View Article : Google Scholar : PubMed/NCBI

Linder MC: Ceruloplasmin and other copper binding components of blood plasma and their functions: An update. Metallomics. 8:887–905. 2016. View Article : Google Scholar : PubMed/NCBI

Moriya M, Ho YH, Grana A, Nguyen L, Alvarez A, Jamil R, Ackland ML, Michalczyk A, Hamer P, Ramos D, et al: Copper is taken up efficiently from albumin and alpha2-macroglobulin by cultured human cells by more than one mechanism. Am J Physiol Cell Physiol. 295:C708–C721. 2008. View Article : Google Scholar : PubMed/NCBI

Liu N, Lo LS, Askary SH, Jones L, Kidane TZ, Trang T, Nguyen M, Goforth J, Chu YH, Vivas E, et al: Transcuprein is a macroglobulin regulated by copper and iron availability. J Nutr Biochem. 18:597–608. 2007. View Article : Google Scholar : PubMed/NCBI

Wang Y, Hodgkinson V, Zhu S, Weisman GA and Petris MJ: Advances in the understanding of mammalian copper transporters. Adv Nutr. 2:129–137. 2011. View Article : Google Scholar :

Chen L, Li N, Zhang M, Sun M, Bian J, Yang B, Li Z, Wang J, Li F, Shi X, et al: APEX2-based proximity labeling of Atox1 Identifies CRIP2 as a nuclear copper-binding protein that regulates autophagy activation. Angew Chem Int Ed Engl. 60:25346–25355. 2021. View Article : Google Scholar : PubMed/NCBI

González-Ballesteros MM, Sánchez-Sánchez L, Espinoza-Guillén A, Espinal-Enríquez J, Mejía C, Hernández-Lemus E and Ruiz-Azuara L: Antitumoral and antimetastatic activity by mixed chelate copper(II) Compounds (Casiopeínas®) on triple-negative breast cancer, in vitro and in vivo models. Int J Mol Sci. 25:88032024. View Article : Google Scholar

Kuo YM, Gybina AA, Pyatskowit JW, Gitschier J and Prohaska JR: Copper transport protein (Ctr1) levels in mice are tissue specific and dependent on copper status. J Nutr. 136:21–26. 2006. View Article : Google Scholar

Vizcaíno C, Mansilla S and Portugal J: Sp1 transcription factor: A long-standing target in cancer chemotherapy. Pharmacol Ther. 152:111–124. 2015. View Article : Google Scholar : PubMed/NCBI

Xue Q, Kang R, Klionsky DJ, Tang D, Liu J and Chen X: Copper metabolism in cell death and autophagy. Autophag. 19:2175–2195. 2023. View Article : Google Scholar

Liang ZD, Tsai WB, Lee MY, Savaraj N and Kuo MT: Specificity protein 1 (sp1) oscillation is involved in copper homeostasis maintenance by regulating human high-affinity copper transporter 1 expression. Mol Pharmacol. 81:455–464. 2012. View Article : Google Scholar :

Ohse VA, Klotz LO and Priebs J: Copper homeostasis in the model organism C. elegans. Cells. 13:7272024. View Article : Google Scholar : PubMed/NCBI

Hatori Y and Lutsenko S: The role of copper chaperone Atox1 in coupling redox homeostasis to intracellular copper distribution. Antioxidants (Basel). 5:252016. View Article : Google Scholar : PubMed/NCBI

Lutsenko S, Barnes NL, Bartee MY and Dmitriev OY: Function and regulation of human copper-transporting ATPases. Physiol Rev. 87:1011–1046. 2007. View Article : Google Scholar : PubMed/NCBI

Sturtz LA, Diekert K, Jensen LT, Lill R and Culotta VC: A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage. J Biol Chem. 276:38084–38089. 2001. View Article : Google Scholar : PubMed/NCBI

Wang Y, Branicky R, Noë A and Hekimi S: Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. 217:1915–1928. 2018. View Article : Google Scholar : PubMed/NCBI

Miriyala S, Spasojevic I, Tovmasyan A, Salvemini D, Vujaskovic Z, St Clair D and Batinic-Haberle I: Manganese superoxide dismutase, MnSOD and its mimics. Biochim Biophys Acta. 1822:794–814. 2012. View Article : Google Scholar :

Boyd SD, Calvo JS, Liu L, Ullrich MS, Skopp A, Meloni G and Winkler DD: The yeast copper chaperone for copper-zinc superoxide dismutase (CCS1) is a multifunctional chaperone promoting all levels of SOD1 maturation. J Biol Chem. 294:1956–1966. 2019. View Article : Google Scholar :

Ding Y, Chen Y, Wu Z, Yang N, Rana K, Meng X, Liu B, Wan H and Qian W: SsCox17, a copper chaperone, is required for pathogenic process and oxidative stress tolerance of Sclerotinia sclerotiorum. Plant Sci. 322:1113452022. View Article : Google Scholar : PubMed/NCBI

Banci L, Bertini I, Ciofi-Baffoni S, Hadjiloi T, Martinelli M and Palumaa P: Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. Proc Natl Acad Sci USA. 105:6803–6808. 2008. View Article : Google Scholar : PubMed/NCBI

Ge EJ, Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, Dou QP, Franz KJ, Gohil VM, Gupta S, et al: Connecting copper and cancer: From transition metal signalling to metalloplasia. Nat Rev Cancer. 22:102–113. 2022. View Article : Google Scholar :

McCann C, Quinteros M, Adelugba I, Morgada MN, Castelblanco AR, Davis EJ, Lanzirotti A, Hainer SJ, Vila AJ, Navea JG and Padilla-Benavides T: The mitochondrial Cu(+) transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro. Front Mol Biosci. 9:10379412022. View Article : Google Scholar : PubMed/NCBI

van Rensburg MJ, van Rooy M, Bester MJ, Serem JC, Venter C and Oberholzer HM: Oxidative and haemostatic effects of copper, manganese and mercury, alone and in combination at physiologically relevant levels: An ex vivo study. Hum Exp Toxicol. 38:419–433. 2019. View Article : Google Scholar

Ruturaj, Mishra M, Saha S, Maji S, Rodriguez-Boulan E, Schreiner R and Gupta A: Regulation of the apico-basolateral trafficking polarity of the homologous copper-ATPases ATP7A and ATP7B. J Cell Sci. 137:jcs2612582024. View Article : Google Scholar

Guttmann S, Nadzemova O, Grünewald I, Lenders M, Brand E, Zibert A and Schmidt HH: ATP7B knockout disturbs copper and lipid metabolism in Caco-2 cells. PLoS One. 15:e02300252020. View Article : Google Scholar : PubMed/NCBI

Dmitriev OY and Patry J: Structure and mechanism of the human copper transporting ATPases: Fitting the pieces into a moving puzzle. Biochim Biophys Acta Biomembr. 1866:1843062024. View Article : Google Scholar : PubMed/NCBI

Percival SS: Copper and immunity. Am J Clin Nutr. 67(5 Suppl): 1064S–1068S. 1998. View Article : Google Scholar : PubMed/NCBI

Jonny, Sitepu EC, Nidom CA, Wirjopranoto S, Sudiana IK, Ansori ANM and Putranto TA: Ex vivo-generated tolerogenic dendritic cells: Hope for a definitive therapy of autoimmune diseases. Curr Issues Mol Biol. 46:4035–4048. 2024. View Article : Google Scholar : PubMed/NCBI

Backal A, Velinov M, Garcia J and Louis CL: Novel, likely pathogenic variant in ATP7A associated with Menkes disease diagnosed with ultrarapid genome sequencing. BMJ Case Rep. 17:e2597922024. View Article : Google Scholar : PubMed/NCBI

Tümer Z and Møller LB: Menkes disease. Eur J Hum Genet. 18:511–518. 2010. View Article : Google Scholar :

Moller LB, Mogensen M, Weaver DD and Pedersen PA: Occipital horn syndrome as a result of splice site mutations in ATP7A. no activity of ATP7A splice variants missing exon 10 or exon 15. Front Mol Neurosci. 14:5322912021. View Article : Google Scholar : PubMed/NCBI

Batzios S, Tal G, DiStasio AT, Peng Y, Charalambous C, Nicolaides P, Kamsteeg EJ, Korman SH, Mandel H, Steinbach PJ, et al: Newly identified disorder of copper metabolism caused by variants in CTR1, a high-affinity copper transporter. Hum Mol Genet. 31:4121–4130. 2022. View Article : Google Scholar : PubMed/NCBI

Garnica A, Chan WY and Rennert O: Copper-histidine treatment of Menkes disease. J Pediatr. 125:336–338. 1994. View Article : Google Scholar : PubMed/NCBI

Moini M, To U and Schilsky ML: Recent advances in Wilson disease. Transl Gastroenterol Hepatol. 6:212021. View Article : Google Scholar : PubMed/NCBI

Weiss KH, Członkowska A, Hedera P and Ferenci P: WTX101 - an investigational drug for the treatment of Wilson disease. Expert Opin Investig Drugs. 27:561–567. 2018. View Article : Google Scholar : PubMed/NCBI

Kreuder J, Otten A, Fuder H, Tümer Z, Tønnesen T, Horn N and Dralle D: Clinical and biochemical consequences of copper-histidine therapy in Menkes disease. Eur J Pediatr. 152:828–832. 1993. View Article : Google Scholar : PubMed/NCBI

Christodoulou J, Danks DM, Sarkar B, Baerlocher KE, Casey R, Horn N, Tümer Z and Clarke JT: Early treatment of Menkes disease with parenteral copper-histidine: Long-term follow-up of four treated patients. Am J Med Genet. 76:154–164. 1998. View Article : Google Scholar : PubMed/NCBI

Ramchandani D, Berisa M, Tavarez DA, Li Z, Miele M, Bai Y, Lee SB, Ban Y, Dephoure N, Hendrickson RC, et al: Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis. Nat Commun. 12:73112021. View Article : Google Scholar : PubMed/NCBI

Xu B, Wang S, Li R, Chen K, He L, Deng M, Kannappan V, Zha J, Dong H and Wang W: Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2. Cell Death Dis. 8:e27972017. View Article : Google Scholar

Theophanides T and Anastassopoulou J: Copper and carcinogenesis. Crit Rev Oncol Hematol. 42:57–64. 2002. View Article : Google Scholar : PubMed/NCBI

Zhong CC, Zhao T, Hogstrand C, Chen F, Song CC and Luo Z: Copper (Cu) induced changes of lipid metabolism through oxidative stress-mediated autophagy and Nrf2/PPARγ pathways. J Nutr Biochem. 100:1088832022. View Article : Google Scholar

Wang Q, Sun Y, Zhao A, Cai X, Yu A, Xu Q, Liu W, Zhang N, Wu S, Chen Y and Wang W: High dietary copper intake induces perturbations in the gut microbiota and affects host ovarian follicle development. Ecotoxicol Environ Saf. 255:1148102023. View Article : Google Scholar : PubMed/NCBI

Tsang T, Posimo JM, Gudiel AA, Cicchini M, Feldser DM and Brady DC: Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nat Cell Biol. 22:412–424. 2020. View Article : Google Scholar : PubMed/NCBI

Conforti RA, Delsouc MB, Zorychta E, Telleria CM and Casais M: Copper in gynecological diseases. Int J Mol Sci. 24:175782023. View Article : Google Scholar : PubMed/NCBI

Compston A: Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver, by S. A. Kinnier Wilson, (From the National Hospital, and the Laboratory of the National Hospital, Queen Square, London) Brain 1912: 34; 295-509. Brain. 132:1997–2001. 2009. View Article : Google Scholar : PubMed/NCBI

Kipker N, Alessi K, Bojkovic M, Padda I and Parmar MS: Neurological-type wilson disease: Epidemiology, clinical manifestations, diagnosis, and management. Cureus. 15:e381702023.PubMed/NCBI

Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH and Schilsky ML: Wilson disease. Nat Rev Dis Primers. 4:212018. View Article : Google Scholar

Kirk FT, Munk DE, Swenson ES, Quicquaro AM, Vendelbo MH, Larsen A, Schilsky ML, Ott P and Sandahl TD: Effects of tetrathiomolybdate on copper metabolism in healthy volunteers and in patients with Wilson disease. J Hepatol. 80:586–595. 2024. View Article : Google Scholar

Bruha R, Marecek Z, Pospisilova L, Nevsimalova S, Vitek L, Martasek P, Nevoral J, Petrtyl J, Urbanek P, Jiraskova A and Ferenci P: Long-term follow-up of Wilson disease: natural history, treatment, mutations analysis and phenotypic correlation. Liver Int. 31:83–91. 2011. View Article : Google Scholar

Członkowska A, Litwin T, Karliński M, Dziezyc K, Chabik G and Czerska M: D-penicillamine versus zinc sulfate as first-line therapy for Wilson's disease. Eur J Neurol. 21:599–606. 2014. View Article : Google Scholar

Brewer GJ: Practical recommendations and new therapies for Wilson's disease. Drugs. 50:240–249. 1995. View Article : Google Scholar : PubMed/NCBI

Xie J, Yang Y, Gao Y and He J: Cuproptosis: Mechanisms and links with cancers. Mol Cancer. 22:462023. View Article : Google Scholar : PubMed/NCBI

Członkowska A and Litwin T: Wilson disease - currently used anticopper therapy. Handb Clin Neurol. 142:181–191. 2017. View Article : Google Scholar

Lambert C, Beraldo H, Lievre N, Garnier-Suillerot A, Dorlet P and Salerno M: Bis(thiosemicarbazone) copper complexes: Mechanism of intracellular accumulation. J Biol Inorg Chem. 18:59–69. 2013. View Article : Google Scholar

Ayton S and Bush AI: β-amyloid: The known unknowns. Ageing Res Rev. 65:1012122021. View Article : Google Scholar

Egan MF, Kost J, Voss T, Mukai Y, Aisen PS, Cummings JL, Tariot PN, Vellas B, van Dyck CH, Boada M, et al: Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease. N Engl J Med. 380:1408–1420. 2019. View Article : Google Scholar : PubMed/NCBI

Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, et al: Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 370:311–321. 2014. View Article : Google Scholar : PubMed/NCBI

Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, et al: Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 370:322–333. 2014. View Article : Google Scholar : PubMed/NCBI

Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, Cummings J and van der Flier WM: Alzheimer's disease. Lancet. 397:1577–1590. 2021. View Article : Google Scholar : PubMed/NCBI

Mazur T, Malik M and Bienko DC: The impact of chelating compounds on Cu(2+), Fe(2+)/(3+), and Zn(2+) ions in Alzheimer's disease treatment. J Inorg Biochem. 257:1126012024. View Article : Google Scholar : PubMed/NCBI

Xu J, Church SJ, Patassini S, Begley P, Waldvogel HJ, Curtis MA, Faull RLM, Unwin RD and Cooper GJS: Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia. Metallomics. 9:1106–1119. 2017. View Article : Google Scholar : PubMed/NCBI

Rembach A, Hare DJ, Lind M, Fowler CJ, Cherny RA, McLean C, Bush AI, Masters CL and Roberts BR: Decreased copper in Alzheimer's disease brain is predominantly in the soluble extractable fraction. Int J Alzheimers Dis. 2013:6232412013.PubMed/NCBI

Scholefield M, Church SJ, Xu J and Cooper GJS: Metallomic analysis of brain tissues distinguishes between cases of dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease dementia. Front Neurosci. 18:14123562024. View Article : Google Scholar : PubMed/NCBI

Squitti R, Simonelli I, Ventriglia M, Siotto M, Pasqualetti P, Rembach A, Doecke J and Bush AI: Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease. J Alzheimers Dis. 38:809–822. 2014. View Article : Google Scholar

Jiao Y and Yang P: Mechanism of copper(II) inhibiting Alzheimer's amyloid beta-peptide from aggregation: A molecular dynamics investigation. J Phys Chem B. 111:7646–7655. 2007. View Article : Google Scholar : PubMed/NCBI

Gomes LM, Vieira RP, Jones MR, Wang MC, Dyrager C, Souza-Fagundes EM, Da Silva JG, Storr T and Beraldo H: 8-Hydroxyquinoline Schiff-base compounds as antioxidants and modulators of copper-mediated Aβ peptide aggregation. J Inorg Biochem. 139:106–116. 2014. View Article : Google Scholar : PubMed/NCBI

Pedersen JT, Østergaard J, Rozlosnik N, Gammelgaard B and Heegaard NH: Cu(II) mediates kinetically distinct, non-amyloidogenic aggregation of amyloid-beta peptides. J Biol Chem. 286:26952–26963. 2011. View Article : Google Scholar : PubMed/NCBI

Reybier K, Ayala S, Alies B, Rodrigues JV, Bustos Rodriguez S, La Penna G, Collin F, Gomes CM, Hureau C and Faller P: Free Superoxide is an intermediate in the production of H2O2 by Copper(I)-Aβ Peptide and O2. Angew Chem Int Ed Engl. 55:1085–1089. 2016. View Article : Google Scholar

Fanlo-Ucar H, Picón-Pagès P, Herrera-Fernández V, Ill-Raga G and Muñoz FJ: The dual role of amyloid beta-peptide in oxidative stress and inflammation: Unveiling Their connections in Alzheimer's disease etiopathology. Antioxidants (Basel). 13:12082024. View Article : Google Scholar : PubMed/NCBI

Xia Y, Dore V, Fripp J, Bourgeat P, Laws SM, Fowler CJ, Rainey-Smith SR, Martins RN, Rowe C, Masters CL, et al: Association of basal forebrain atrophy with cognitive decline in early Alzheimer disease. Neurology. 103:e2096262024. View Article : Google Scholar : PubMed/NCBI

Lang M, Fan Q, Wang L, Zheng Y, Xiao G, Wang X, Wang W, Zhong Y and Zhou B: Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer's disease-like symptoms. Neurobiol Aging. 34:2604–2612. 2013. View Article : Google Scholar : PubMed/NCBI

Ceccom J, Coslédan F, Halley H, Francès B, Lassalle JM and Meunier B: Copper chelator induced efficient episodic memory recovery in a non-transgenic Alzheimer's mouse model. PLoS One. 2012(7): e431052012. View Article : Google Scholar

Quinn JF, Harris CJ, Cobb KE, Domes C, Ralle M, Brewer G and Wadsworth TL: A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 21:903–914. 2010. View Article : Google Scholar : PubMed/NCBI

Chen C, Jiang X, Li Y, Yu H, Li S, Zhang Z, Xu H, Yang Y, Liu G, Zhu F, et al: Low-dose oral copper treatment changes the hippocampal phosphoproteomic profile and perturbs mitochondrial function in a mouse model of Alzheimer's disease. Free Radic Biol Med. 135:144–156. 2019. View Article : Google Scholar : PubMed/NCBI

Yao D, Jing T, Niu L, Huang X, Wang Y, Deng X and Wang M: Amyloidogenesis induced by diet cholesterol and copper in a model mouse for Alzheimer's disease and protection effects of zinc and fluvastatin. Brain Res Bull. 143:1–8. 2018. View Article : Google Scholar : PubMed/NCBI

Maynard CJ, Cappai R, Volitakis I, Laughton KM, Masters CL, Bush AI and Li QX: Chronic exposure to high levels of zinc or copper has little effect on brain metal homeostasis or Abeta accumulation in transgenic APP-C100 mice. Cell Mol Neurobiol. 29:757–767. 2009. View Article : Google Scholar : PubMed/NCBI

Acevedo KM, Hung YH, Dalziel AH, Li QX, Laughton K, Wikhe K, Rembach A, Roberts B, Masters CL, Bush AI and Camakaris J: Copper promotes the trafficking of the amyloid precursor protein. J Biol Chem. 286:8252–8262. 2011. View Article : Google Scholar :

Borchardt T, Camakaris J, Cappai R, Masters CL, Beyreuther K and Multhaup G: Copper inhibits beta-amyloid production and stimulates the non-amyloidogenic pathway of amyloid-precursor-protein secretion. Biochem J. 344:461–467. 1999. View Article : Google Scholar : PubMed/NCBI

Afsar A, Chacon Castro MDC, Soladogun AS and Zhang L: Recent development in the understanding of molecular and cellular mechanisms underlying the etiopathogenesis of Alzheimer's disease. Int J Mol Sci. 24:72582023. View Article : Google Scholar : PubMed/NCBI

Wang Y, Chen Y, Zhang J, Yang Y, Fleishman JS, Wang Y, Wang J, Chen J, Li Y and Wang H: Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance. Drug Resist Updat. 72:1010182024. View Article : Google Scholar

Kumar V, Singh AP, Wheeler N, Galindo CL and Kim JJ: Safety profile of D-penicillamine: A comprehensive pharmacovigilance analysis by FDA adverse event reporting system. Expert Opin Drug Saf. 20:1443–1450. 2021. View Article : Google Scholar : PubMed/NCBI

Lee EJ, Woo MH, Moon JS and Ko JS: Efficacy and safety of D-penicillamine, trientine, and zinc in pediatric Wilson disease patients. Orphanet J Rare Dis. 19:2612024. View Article : Google Scholar : PubMed/NCBI

Perez DR, Sklar LA and Chigaev A: Clioquinol: To harm or heal. Pharmacol Ther. 199:155–163. 2019. View Article : Google Scholar : PubMed/NCBI

Relkin N: Testing the mettle of PBT2 for Alzheimer's disease. Lancet Neurol. 7:762–763. 2008. View Article : Google Scholar : PubMed/NCBI

Daniel KG, Chen D, Orlu S, Cui QC, Miller FR and Dou QP: Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells. Breast Cancer Res. 7:R897–R908. 2005. View Article : Google Scholar : PubMed/NCBI

Crouch PJ, Hung LW, Adlard PA, Cortes M, Lal V, Filiz G, Perez KA, Nurjono M, Caragounis A, Du T, et al: Increasing Cu bioavailability inhibits Abeta oligomers and tau phosphorylation. Proc Natl Acad Sci USA. 106:381–386. 2009. View Article : Google Scholar : PubMed/NCBI

Schimmer AD: Clioquinol - a novel copper-dependent and independent proteasome inhibitor. Curr Cancer Drug Targets. 11:325–331. 2011. View Article : Google Scholar : PubMed/NCBI

Costello LC and Franklin RB: A proposed efficacious treatment with clioquinol (Zinc Ionophore) and Cabergoline (Prolactin Dopamine Agonist) for the treatment of terminal androgen-independent prostate cancer. Why and How? J Clin Res Oncol. Feb 27–2019.Epub ahead of print. PubMed/NCBI

Donnelly PS, Caragounis A, Du T, Laughton KM, Volitakis I, Cherny RA, Sharples RA, Hill AF, Li QX, Masters CL, et al: Selective intracellular release of copper and zinc ions from bis(thiosemicarbazonato) complexes reduces levels of Alzheimer disease amyloid-beta peptide. J Biol Chem. 283:4568–4577. 2008. View Article : Google Scholar

Drew SC: Chelator PBT2 forms a ternary Cu(2+) Complex with β-Amyloid That has high stability but low specificity. Int J Mol Sci. 24:92672023. View Article : Google Scholar

Scholefield M, Patassini S, Xu J and Cooper GJS: Widespread selenium deficiency in the brain of cases with Huntington's disease presents a new potential therapeutic target. Ebiomedicine. 97:1048242023. View Article : Google Scholar : PubMed/NCBI

Upadhyay A, Chhangani D, Rao NR, Kofler J, Vassar R, Rincon-Limas DE and Savas JN: Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity. Mol Neurodegener. 18:612023. View Article : Google Scholar : PubMed/NCBI

Hands SL, Mason R, Sajjad MU, Giorgini F and Wyttenbach A: Metallothioneins and copper metabolism are candidate therapeutic targets in Huntington's disease. Biochem Soc Trans. 38:552–558. 2010. View Article : Google Scholar : PubMed/NCBI

Zhu Z, Song M, Ren J, Liang L, Mao G and Chen M: Copper homeostasis and cuproptosis in central nervous system diseases. Cell Death Dis. 15:8502024. View Article : Google Scholar : PubMed/NCBI

Cherny RA, Ayton S, Finkelstein DI, Bush AI, McColl G and Massa SM: PBT2 Reduces Toxicity in a C. elegans Model of polyQ aggregation and extends lifespan, reduces striatal atrophy and improves motor performance in the R6/2 mouse model of Huntington's disease. J Huntingtons Dis. 1:211–219. 2012. View Article : Google Scholar : PubMed/NCBI

Rodriguez-Oroz MC, Jahanshahi M, Krack P, Litvan I, Macias R, Bezard E and Obeso JA: Initial clinical manifestations of Parkinson's disease: Features and pathophysiological mechanisms. Lancet Neurol. 8:1128–1139. 2009. View Article : Google Scholar : PubMed/NCBI

Davies KM, Hare DJ, Cottam V, Chen N, Hilgers L, Halliday G, Mercer JF and Double KL: Localization of copper and copper transporters in the human brain. Metallomics. 5:43–51. 2013. View Article : Google Scholar

Dexter DT, Wells FR, Lees AJ, Agid F, Agid Y, Jenner P and Marsden CD: Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. J Neurochem. 52:1830–1836. 1989. View Article : Google Scholar : PubMed/NCBI

Ayton S, Lei P, Duce JA, Wong BX, Sedjahtera A, Adlard PA, Bush AI and Finkelstein DI: Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease. Ann Neurol. 73:554–559. 2013. View Article : Google Scholar : PubMed/NCBI

Bisaglia M and Bubacco L: Copper ions and Parkinson's disease: Why Is homeostasis so relevant? Biomolecules. 10:1952020. View Article : Google Scholar : PubMed/NCBI

Hemmati-Dinarvand M, Saedi S, Valilo M, Kalantary-Charvadeh A, Alizadeh Sani M, Kargar R, Safari H and Samadi N: Oxidative stress and Parkinson's disease: Conflict of oxidant-antioxidant systems. Neurosci Lett. 709:1342962019. View Article : Google Scholar : PubMed/NCBI

Trist BG, Davies KM, Cottam V, Genoud S, Ortega R, Roudeau S, Carmona A, De Silva K, Wasinger V, Lewis SJG, et al: Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson's disease brain. Acta Neuropathol. 134:113–127. 2017. View Article : Google Scholar : PubMed/NCBI

Zhang MS, Liang JH, Yang MJ, Ren YR, Cheng DH, Wu QH, He Y and Yin J: Low serum superoxide dismutase is associated with a high risk of cognitive impairment after mild acute ischemic stroke. Front Aging Neurosci. 14:8341142022. View Article : Google Scholar : PubMed/NCBI

Quinn PMJ, Moreira PI, Ambrósio AF and Alves CH: PINK1/PARKIN signalling in neurodegeneration and neuroinflammation. Acta Neuropathol Commun. 8:1892020. View Article : Google Scholar : PubMed/NCBI

Cummins N and Götz J: Shedding light on mitophagy in neurons: What is the evidence for PINK1/Parkin mitophagy in vivo? Cell Mol Life Sci. 75:1151–1162. 2018. View Article : Google Scholar

Aschner M, Skalny AV, Lu R, Martins AC, Tizabi Y, Nekhoroshev SV, Santamaria A, Sinitskiy AI and Tinkov AA: Mitochondrial pathways of copper neurotoxicity: Focus on mitochondrial dynamics and mitophagy. Front Mol Neurosci. 17:15048022024. View Article : Google Scholar : PubMed/NCBI

Ling Z, Ge X, Jin C, Song Z, Zhang H, Fu Y, Zheng K, Xu R and Jiang H: Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration. Bioact Mater. 46:195–212. 2024.

Synhaivska O, Bhattacharya S, Campioni S, Thompson D and Nirmalraj PN: Single-particle resolution of copper-associated annular α-synuclein oligomers reveals potential therapeutic targets of neurodegeneration. ACS Chem Neurosci. 13:1410–1421. 2022. View Article : Google Scholar : PubMed/NCBI

Triscott J, Rose Pambid M and Dunn SE: Concise review: Bullseye: Targeting cancer stem cells to improve the treatment of gliomas by repurposing disulfiram. Stem Cells. 33:1042–1046. 2015. View Article : Google Scholar : PubMed/NCBI

Kannappan V, Ali M, Small B, Rajendran G, Elzhenni S, Taj H, Wang W and Dou QP: Recent advances in repurposing disulfiram and disulfiram derivatives as copper-dependent anticancer agents. Front Mol Biosci. 8:7413162021. View Article : Google Scholar : PubMed/NCBI

Zhou Q, Zhang Y, Lu L, Zhang H, Zhao C, Pu Y and Yin L: Copper induces microglia-mediated neuroinflammation through ROS/NF-κB pathway and mitophagy disorder. Food Chem Toxicol. 168:1133692022. View Article : Google Scholar

Chidambaram SB, Anand N, Varma SR, Ramamurthy S, Vichitra C, Sharma A, Mahalakshmi AM and Essa MM: Superoxide dismutase and neurological disorders. IBRO Neurosci Rep. 16:373–394. 2024. View Article : Google Scholar : PubMed/NCBI

Cukierman DS, Pinheiro AB, Castiñeiras-Filho SL, da Silva AS, Miotto MC, De Falco A, de P Ribeiro T, Maisonette S, da Cunha AL, Hauser-Davis RA, et al: A moderate metal-binding hydrazone meets the criteria for a bioinorganic approach towards Parkinson's disease: Therapeutic potential, blood-brain barrier crossing evaluation and preliminary toxicological studies. J Inorg Biochem. 170:160–168. 2017. View Article : Google Scholar : PubMed/NCBI

Vavere AL and Lewis JS: Cu-ATSM: A radiopharmaceutical for the PET imaging of hypoxia. Dalton Trans. 4893–4902. 2007. View Article : Google Scholar : PubMed/NCBI

Ikawa M, Okazawa H, Kudo T, Kuriyama M, Fujibayashi Y and Yoneda M: Evaluation of striatal oxidative stress in patients with Parkinson's disease using [62Cu]ATSM PET. Nucl Med Biol. 38:945–951. 2011. View Article : Google Scholar : PubMed/NCBI

Hung LW, Villemagne VL, Cheng L, Sherratt NA, Ayton S, White AR, Crouch PJ, Lim S, Leong SL, Wilkins S, et al: The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease. J Exp Med. 209:837–854. 2012. View Article : Google Scholar : PubMed/NCBI

Rowlands BD, Trist BG, Karozis C, Schaffer G, Mor D, Harwood R, Rosolen SA, Cottam V, Persson-Carboni F, Richardson M, et al: Copper supplementation mitigates Parkinson-like wild-type SOD1 pathology and nigrostriatal degeneration in a novel mouse model. Acta Neuropathol Commun. 13:1332025. View Article : Google Scholar : PubMed/NCBI

Al-Chalabi A and Hardiman O: The epidemiology of ALS: A conspiracy of genes, environment and time. Nat Rev Neurol. 9:617–628. 2013. View Article : Google Scholar : PubMed/NCBI

Min JH, Sarlus H and Harris RA: Copper toxicity and deficiency: The vicious cycle at the core of protein aggregation in ALS. Front Mol Neurosci. 17:14081592024. View Article : Google Scholar : PubMed/NCBI

Moriyama H and Yokota T: Recent progress of antisense oligonucleotide therapy for superoxide-dismutase-1-mutated amyotrophic lateral sclerosis: Focus on tofersen. Genes (Basel). 15:13422024. View Article : Google Scholar : PubMed/NCBI

Jerusalem F, Pohl C, Karitzky J and Ries F: ALS. Neurology. 47(Suppl 4): S218–S220. 1996. View Article : Google Scholar : PubMed/NCBI

Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX, et al: Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science. 264:1772–1775. 1994. View Article : Google Scholar : PubMed/NCBI

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I and Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 74:229–263. 2024.PubMed/NCBI

Ansori ANM, Widyananda MH, Antonius Y, Murtadlo AAA, Kharisma VD, Wiradana PA, Sahadewa S, Durry FD, Maksimiuk N, Rebezov M and Zainul R: A review of cancer-related hypercalcemia: Pathophysiology, current treatments, and future directions. J Med Pharm Chem Res. 6:944–952. 2024.

Wu T, Sempos CT, Freudenheim JL, Muti P and Smit E: Serum iron, copper and zinc concentrations and risk of cancer mortality in US adults. Ann Epidemiol. 14:195–201. 2004. View Article : Google Scholar : PubMed/NCBI

Hyvönen MT, Ucal S, Pasanen M, Peräniemi S, Weisell J, Khomutov M, Khomutov AR, Vepsäläinen J, Alhonen L and Keinänen TA: Triethylenetetramine modulates polyamine and energy metabolism and inhibits cancer cell proliferation. Biochem J. 473:1433–1441. 2016. View Article : Google Scholar : PubMed/NCBI

Pavithra V, Sathisha TG, Kasturi K, Mallika DS, Amos SJ and Ragunatha S: Serum levels of metal ions in female patients with breast cancer. J Clin Diagn Res. 9:BC25–c27. 2015.PubMed/NCBI

Jakhmola V, Parashar T, Ghildiyal P, Ansori ANM, Sharma RK, Rao NGR, Kalra K, Singh N, Nainwal N, Singh RK, et al: An in silico study to explore the role of EGFR in ovarian cancer. Pharmacog J. 14:817–821. 2022. View Article : Google Scholar

Zhang X and Yang Q: Association between serum copper levels and lung cancer risk: A meta-analysis. J Int Med Res. 46:4863–4873. 2018. View Article : Google Scholar : PubMed/NCBI

Saleh SAK, Adly HM, Abdelkhaliq AA and Nassir AM: Serum levels of selenium, zinc, copper, manganese, and iron in prostate cancer patients. Curr Urol. 14:44–49. 2020. View Article : Google Scholar : PubMed/NCBI

Atakul T, Altinkaya SO, Abas BI and Yenisey C: Serum copper and zinc levels in patients with endometrial cancer. Biol Trace Elem Res. 195:46–54. 2020. View Article : Google Scholar

Fang AP, Chen PY, Wang XY, Liu ZY, Zhang DM, Luo Y, Liao GC, Long JA, Zhong RH, Zhou ZG, et al: Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong liver cancer cohort. Int J Cancer. 144:2823–2832. 2019. View Article : Google Scholar

Lun X, Wells JC, Grinshtein N, King JC, Hao X, Dang NH, Wang X, Aman A, Uehling D, Datti A, et al: Disulfiram when combined with copper enhances the therapeutic effects of temozolomide for the treatment of glioblastoma. Clin Cancer Res. 22:3860–3875. 2016. View Article : Google Scholar : PubMed/NCBI

Li Y, Chen F, Chen J, Chan S, He Y, Liu W and Zhang G: Disulfiram/copper induces antitumor activity against both nasopharyngeal cancer cells and cancer-associated fibroblasts through ROS/MAPK and ferroptosis pathways. Cancers (Basel). 12:1382020. View Article : Google Scholar : PubMed/NCBI

Mcauslan BR and Reilly W: Endothelial cell phagokinesis in response to specific metal ions. Exp Cell Res. 130:147–157. 1980. View Article : Google Scholar : PubMed/NCBI

Narayanan G, R BS, Vuyyuru H, Muthuvel B and Konerirajapuram Natrajan S: CTR1 Silencing inhibits angiogenesis by limiting copper entry into endothelial cells. PLoS One. 8:e719822013. View Article : Google Scholar : PubMed/NCBI

Mandinov L, Mandinova A, Kyurkchiev S, Kyurkchiev D, Kehayov I, Kolev V, Soldi R, Bagala C, de Muinck ED, Lindner V, et al: Copper chelation represses the vascular response to injury. Proc Natl Acad Sci USA. 100:6700–6705. 2003. View Article : Google Scholar : PubMed/NCBI

Nurzynska A, Klimek K, Swierzycka I, Palka K and Ginalska G: Porous curdlan-based hydrogels modified with copper ions as potential dressings for prevention and management of bacterial wound infection-an in vitro assessment. Polymers (Basel). 12:18932020. View Article : Google Scholar : PubMed/NCBI

Badet J, Soncin F, Guitton JD, Lamare O, Cartwright T and Barritault D: Specific binding of angiogenin to calf pulmonary artery endothelial cells. Proc Natl Acad Sci USA. 86:8427–8431. 1989. View Article : Google Scholar : PubMed/NCBI

Zhao YN, Chen LH, Yang XL, Dong JY, Wu WB, Chen D, Geng RM, Ke NW and Liu J: Inhibition of copper transporter-1 by ammonium tetrathiocarbolybdate in the treatment of pancreatic cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 51:643–649. 2020.In Chinese. PubMed/NCBI

Pan Q, Bao LW and Merajver SD: Tetrathiomolybdate inhibits angiogenesis and metastasis through suppression of the NFkappaB signaling cascade. Mol Cancer Res. 1:701–706. 2003.PubMed/NCBI

Pan Q, Kleer CG, van Golen KL, Irani J, Bottema KM, Bias C, De Carvalho M, Mesri EA, Robins DM, Dick RD, et al: Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis. Cancer Res. 62:4854–4859. 2002.PubMed/NCBI

Li Y, Fang M, Xu Z and Li X: Tetrathiomolybdate as an old drug in a new use: As a chemotherapeutic sensitizer for non-small cell lung cancer. J Inorg Biochem. 233:1118652022. View Article : Google Scholar : PubMed/NCBI

Crowe A, Jackaman C, Beddoes KM, Ricciardo B and Nelson DJ: Rapid copper acquisition by developing murine mesothelioma: Decreasing bioavailable copper slows tumor growth, normalizes vessels and promotes T cell infiltration. PLoS One. 8:e736842013. View Article : Google Scholar : PubMed/NCBI

Cosimo RD, Scarpelli A, Lappano R, Pisano A, Santolla MF, De Marco P, Cirillo F, Cappello AR, Dolce V, Belfiore A, et al: Copper activates HIF-1α/GPER/VEGF signalling in cancer cells. Oncotarget. 6:34158–34177. 2015. View Article : Google Scholar

Mammoto T, Jiang A, Jiang E, Panigrahy D, Kieran MW and Mammoto A: Role of collagen matrix in tumor angiogenesis and glioblastoma multiforme progression. Am J Pathol. 183:1293–1305. 2013. View Article : Google Scholar : PubMed/NCBI

Baldari S, Di Rocco G, Heffern MC, Su TA, Chang CJ and Toietta G: Effects of copper chelation on BRAF(V600E) positive colon carcinoma cells. Cancers (Basel). 11:6592019. View Article : Google Scholar : PubMed/NCBI

Brady DC, Crowe MS, Turski ML, Hobbs GA, Yao X, Chaikuad A, Knapp S, Xiao K, Campbell SL, Thiele DJ and Counter CM: Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature. 509:492–496. 2014. View Article : Google Scholar : PubMed/NCBI

Brady DC, Crowe MS, Greenberg DN and Counter CM: Copper chelation inhibits BRAFV600E-driven melanomagenesis and counters resistance to BRAFV600E and MEK1/2 inhibitors. Cancer Res. 77:6240–6252. 2017. View Article : Google Scholar : PubMed/NCBI

Ross MO, Xie Y, Owyang RC, Ye C, Zbihley ONP, Lyu R, Wu T, Wang P, Karginova O, Olopade OI, et al: PTPN2 copper-sensing relays copper level fluctuations into EGFR/CREB activation and associated CTR1 transcriptional repression. Nat Commun. 15:69472024. View Article : Google Scholar : PubMed/NCBI

Voli F, Valli E, Lerra L, Kimpton K, Saletta F, Giorgi FM, Mercatelli D, Rouaen JRC, Shen S, Murray JE, et al: Intratumoral copper modulates PD-L1 expression and influences tumor immune evasion. Cancer Res. 80:4129–4144. 2020. View Article : Google Scholar : PubMed/NCBI

Xu M, Casio M, Range DE, Sosa JA and Counter CM: Copper chelation as targeted therapy in a mouse model of oncogenic BRAF-Driven papillary thyroid cancer. Clin Cancer Res. 24:4271–4281. 2018. View Article : Google Scholar : PubMed/NCBI

Akins NS, Nielson TC and Le HV: Inhibition of glycolysis and glutaminolysis: An emerging drug discovery approach to combat cancer. Curr Top Med Chem. 18:494–504. 2018. View Article : Google Scholar : PubMed/NCBI

Carneiro BA and El-Deiry WS: Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol. 17:395–417. 2020. View Article : Google Scholar : PubMed/NCBI

Achmad AB, Proboningrat A, Ansori ANM, Fadholly A, Rochmi SE, Samsudin RR, Hidayatik N, Hendarti GA and Jayanti S: Stem bark ethanolic extract of Pinus merkusii induces caspase 9-mediated apoptosis in HeLa cells. Open Vet J. 14:2628–2633. 2024. View Article : Google Scholar : PubMed/NCBI

Weinlich R, Oberst A, Beere HM and Green DR: Necroptosis in development, inflammation and disease. Nat Rev Mol Cell Biol. 18:127–136. 2017. View Article : Google Scholar

Bergsbaken T, Fink SL and Cookson BT: Pyroptosis: Host cell death and inflammation. Nat Rev Microbiol. 7:99–109. 2009. View Article : Google Scholar : PubMed/NCBI

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI

Gao W, Huang Z, Duan J, Nice EC, Lin J and Huang C: Elesclomol induces copper-dependent ferroptosis in colorectal cancer cells via degradation of ATP7A. Mol Oncol. 15:3527–3544. 2021. View Article : Google Scholar : PubMed/NCBI

Pan C, Ji Z, Wang Q, Zhang Z, Wang Z, Li C, Lu S and Ge P: Cuproptosis: Mechanisms, biological significance, and advances in disease treatment-A systematic review. CNS Neurosci Ther. 30:e700392024. View Article : Google Scholar : PubMed/NCBI

Huang Z, Wang L, Chen L, Zhang Y and Shi P: Induction of cell cycle arrest via the p21, p27-cyclin E,A/Cdk2 pathway in SMMC-7721 hepatoma cells by clioquinol. Acta Pharm. 65:463–471. 2015. View Article : Google Scholar : PubMed/NCBI

Tsvetkov P, Detappe A, Cai K, Keys HR, Brune Z, Ying W, Thiru P, Reidy M, Kugener G, Rossen J, et al: Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 15:681–689. 2019. View Article : Google Scholar : PubMed/NCBI

Tardito S, Bassanetti I, Bignardi C, Elviri L, Tegoni M, Mucchino C, Bussolati O, Franchi-Gazzola R and Marchiò L: Copper binding agents acting as copper ionophores lead to caspase inhibition and paraptotic cell death in human cancer cells. J Am Chem Soc. 133:6235–6242. 2011. View Article : Google Scholar : PubMed/NCBI

Tardito S, Barilli A, Bassanetti I, Tegoni M, Bussolati O, Franchi-Gazzola R, Mucchino C and Marchiò L: Copper-dependent cytotoxicity of 8-hydroxyquinoline derivatives correlates with their hydrophobicity and does not require caspase activation. J Med Chem. 55:10448–10459. 2012. View Article : Google Scholar : PubMed/NCBI

Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, Chu J, Beaudette-Zlatanova BC, Lu R, Blackman RK, Barsoum J, et al: The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med. 52:2142–2150. 2012. View Article : Google Scholar : PubMed/NCBI

Shimada K, Reznik E, Stokes ME, Krishnamoorthy L, Bos PH, Song Y, Quartararo CE, Pagano NC, Carpizo DR, deCarvalho AC, et al: Copper-binding small molecule induces oxidative stress and cell-cycle arrest in glioblastoma-patient-derived cells. Cell Chem Biol. 25:585–594 e7. 2018. View Article : Google Scholar : PubMed/NCBI

Yip NC, Fombon IS, Liu P, Brown S, Kannappan V, Armesilla AL, Xu B, Cassidy J, Darling JL and Wang W: Disulfiram modulated ROS-MAPK and NFĸB pathways and targeted breast cancer cells with cancer stem cell-like properties. Br J Cancer. 104:1564–1574. 2011. View Article : Google Scholar : PubMed/NCBI

Chen D, Cui QC, Yang H and Dou QP: Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 66:10425–10433. 2006. View Article : Google Scholar : PubMed/NCBI

Liu N, Huang H, Dou QP and Liu J: Inhibition of 19S proteasome-associated deubiquitinases by metal-containing compounds. Oncoscience. 2:457–466. 2015. View Article : Google Scholar : PubMed/NCBI

Baldari S, Di Rocco G and Toietta G: Current biomedical use of copper chelation therapy. Int J Mol Sci. 21:10692020. View Article : Google Scholar : PubMed/NCBI

Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, Rossen J, Joesch-Cohen L, Humeidi R, Spangler RD, et al: Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 375:1254–1261. 2022. View Article : Google Scholar : PubMed/NCBI

Li P, Sun Q, Bai S, Wang H and Zhao L: Combination of the cuproptosis inducer disulfiram and anti-PD-L1 abolishes NSCLC resistance by ATP7B to regulate the HIF-1 signaling pathway. Int J Mol Med. 53:192024. View Article : Google Scholar :

Huang N, Feng Y, Liu Y, Zhang Y, Liu L, Zhang B, Zhang T, Su Z, Xue L and Wu ZB: Disulfiram mediated anti-tumour effect in pituitary neuroendocrine tumours by inducing cuproptosis. Int Immunopharmacol. 134:1121592024. View Article : Google Scholar : PubMed/NCBI

Guo B, Yang F, Zhang L, Zhao Q, Wang W, Yin L, Chen D, Wang M, Han S, Xiao H and Xing N: Cuproptosis induced by ROS responsive nanoparticles with elesclomol and copper combined with αPD-L1 for enhanced cancer immunotherapy. Adv Mater. 35:e22122672023. View Article : Google Scholar

Sun L, Zhang Y, Yang B, Sun S, Zhang P, Luo Z, Feng T, Cui Z, Zhu T, Li Y, et al: Lactylation of METTL16 promotes cuproptosis via m(6)A-modification on FDX1 mRNA in gastric cancer. Nat Commun. 14:65232023. View Article : Google Scholar : PubMed/NCBI

Buccarelli M, D'Alessandris QG, Matarrese P, Mollinari C, Signore M, Cappannini A, Martini M, D'Aliberti P, De Luca G, Pedini F, et al: Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth. J Exp Clin Cancer Res. 40:2282021. View Article : Google Scholar : PubMed/NCBI

Solmonson A and DeBerardinis RJ: Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 293:7522–7530. 2018. View Article : Google Scholar :

Harris IS, Endress JE, Coloff JL, Selfors LM, McBrayer SK, Rosenbluth JM, Takahashi N, Dhakal S, Koduri V, Oser MG, et al: Deubiquitinases maintain protein homeostasis and survival of cancer cells upon glutathione depletion. Cell Metab. 29:1166–1181.e6. 2019. View Article : Google Scholar : PubMed/NCBI

Zhou S, Kachhap S and Singh KK: Mitochondrial impairment in p53-deficient human cancer cells. Mutagenesis. 18:287–292. 2003. View Article : Google Scholar : PubMed/NCBI

Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F and Hwang PM: p53 regulates mitochondrial respiration. Science. 312:1650–1653. 2006. View Article : Google Scholar : PubMed/NCBI

Saleem A, Adhihetty PJ and Hood DA: Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle. Physiol Genomics. 37:58–66. 2009. View Article : Google Scholar

Zhang C, Lin M, Wu R, Wang X, Yang B, Levine AJ, Hu W and Feng Z: Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci USA. 108:16259–16264. 2011. View Article : Google Scholar : PubMed/NCBI

Contractor T and Harris CR: p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2. Cancer Res. 72:560–567. 2012. View Article : Google Scholar

Bischoff ME, Shamsaei B, Yang J, Secic D, Vemuri B, Reisz JA, D'Alessandro A, Bartolacci C, Adamczak R, Schmidt L, et al: Copper drives remodeling of metabolic state and progression of clear cell renal cell carcinoma. Cancer Discov. 15:401–426. 2025. View Article : Google Scholar :

Gan Y, Liu T, Feng W, Wang L, Li LI and Ning Y: Drug repositioning of disulfiram induces endometrioid epithelial ovarian cancer cell death via the both apoptosis and cuproptosis pathways. Oncol Res. 31:333–343. 2023. View Article : Google Scholar : PubMed/NCBI

Liu X, Luo B, Wu X and Tang Z: Cuproptosis and cuproptosis-related genes: Emerging potential therapeutic targets in breast cancer. Biochim Biophys Acta Rev Cancer. 1878:1890132023. View Article : Google Scholar : PubMed/NCBI

Liu T, Zhou Z, Zhang M, Lang P, Li J, Liu Z, Zhang Z, Li L and Zhang L: Cuproptosis-immunotherapy using PD-1 overexpressing T cell membrane-coated nanosheets efficiently treats tumor. J Control Release. 362:502–512. 2023. View Article : Google Scholar : PubMed/NCBI

Lu X, Deng W, Wang S, Zhao S, Zhu B, Bai B, Mao Y, Lin J, Yi Y, Xie Z, et al: PEGylated Elesclomol@Cu(II)-based Metal-organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy. Mater Today Bio. 29:1013172024. View Article : Google Scholar

Hasinoff BB, Wu X, Yadav AA, Patel D, Zhang H, Wang DS, Chen ZS and Yalowich JC: Cellular mechanisms of the cytotoxicity of the anticancer drug elesclomol and its complex with Cu(II). Biochem Pharmacol. 93:266–276. 2015. View Article : Google Scholar : PubMed/NCBI

Jiao Y, Hannafon BN and Ding WQ: Disulfiram's anticancer activity: Evidence and mechanisms. Anticancer Agents Med Chem. 16:1378–1384. 2016. View Article : Google Scholar : PubMed/NCBI

Xie L, Gong J, He Z, Zhang W and Wang H, Wu S, Wang X, Sun P, Cai L, Wu Z and Wang H: A copper-manganese based nanocomposite induces cuproptosis and potentiates anti-tumor immune responses. Small. 21:e24121742025. View Article : Google Scholar : PubMed/NCBI

Deng L, Liu T, Liu CA, Zhang Q, Song MM, Lin SQ, Wang YM, Zhang QS and Shi HP: The association of metabolic syndrome score trajectory patterns with risk of all cancer types. Cancer. 130:2150–2159. 2024. View Article : Google Scholar : PubMed/NCBI

Song M, Liu T, Liu H, Zhang Q, Zhang Q, Wang Y, Ma X, Cao L and Shi H: Association between metabolic syndrome, C-reactive protein, and the risk of primary liver cancer: A large prospective study. BMC Cancer. 22:8532022. View Article : Google Scholar : PubMed/NCBI

Gathirua-Mwangi WG, Song Y, Monahan PO, Champion VL and Zollinger TW: Associations of metabolic syndrome and C-reactive protein with mortality from total cancer, obesity-linked cancers and breast cancer among women in NHANES III. Int J Cancer. 143:535–542. 2018. View Article : Google Scholar : PubMed/NCBI

Springer C, Humayun D and Skouta R: Cuproptosis: Unraveling the mechanisms of copper-induced cell death and its implication in cancer therapy. Cancers (Basel). 16:6472024. View Article : Google Scholar : PubMed/NCBI

Chen Z, Li Y, Yin Y, Song M, Wang F and Jiang G: Cu Nanowires trigger efficient cuproptosis via special intracellular distribution and excessive Cu Ion release. Nano Lett. 24:11446–11453. 2024. View Article : Google Scholar : PubMed/NCBI

Shao R, Visser I, Fros JJ and Yin X: Versatility of the zinc-finger antiviral protein (ZAP) As a modulator of viral infections. Int J Biol Sci. 20:4585–4600. 2024. View Article : Google Scholar : PubMed/NCBI

Zhang N, Yu X, Xie J and Xu H: New insights into the role of ferritin in iron homeostasis and neurodegenerative diseases. Mol Neurobiol. 58:2812–2823. 2021. View Article : Google Scholar : PubMed/NCBI

Ermini ML and Voliani V: Antimicrobial nano-agents: The copper age. ACS Nano. 15:6008–6029. 2021. View Article : Google Scholar : PubMed/NCBI

Lu X, Chen X, Lin C, Yi Y, Zhao S, Zhu B, Deng W, Wang X, Xie Z, Rao S, et al: Elesclomol loaded copper oxide nanoplatform triggers cuproptosis to enhance antitumor immunotherapy. Adv Sci (Weinh). 11:e23099842024. View Article : Google Scholar : PubMed/NCBI

Zheng P, Zhou C, Lu L, Liu B and Ding Y: Elesclomol: A copper ionophore targeting mitochondrial metabolism for cancer therapy. J Exp Clin Cancer Res. 41:2712022. View Article : Google Scholar : PubMed/NCBI

Woźniak-Budych MJ, Staszak K and Staszak M: Copper and copper-based nanoparticles in medicine-perspectives and challenges. Molecules. 28:66872023. View Article : Google Scholar

Brewer GJ: Tetrathiomolybdate anticopper therapy for Wilson's disease inhibits angiogenesis, fibrosis and inflammation. J Cell Mol Med. 7:11–20. 2003. View Article : Google Scholar : PubMed/NCBI

Kim YJ, Tsang T, Anderson GR, Posimo JM and Brady DC: Inhibition of BCL2 family members increases the efficacy of copper chelation in BRAFV600E-Driven melanoma. Cancer Res. 80:1387–1400. 2020. View Article : Google Scholar : PubMed/NCBI

Ishida S, McCormick F, Smith-McCune K and Hanahan D: Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator. Cancer Cell. 17:574–583. 2010. View Article : Google Scholar : PubMed/NCBI

Lin X, Chen W, Li B, Zhao Z, Yu Z, Zhao XY, Zhou X, Feng Z, Lin C and Cao W: Targeting intratumoral copper inhibits tumor progression via p62-Mediated EZH2 degradation and potentiates Anti-PD-1 immunotherapy in oral squamous cell carcinoma. Adv Sci (Weinh). Jul 28–2025.Epub ahead of print. View Article : Google Scholar

Xue Q, Yan D, Chen X, Li X, Kang R, Klionsky DJ, Kroemer G, Chen X, Tang D and Liu J: Copper-dependent autophagic degradation of GPX4 drives ferroptosis. Autophagy. 19:1982–1996. 2023. View Article : Google Scholar : PubMed/NCBI

Li F, Wu X, Liu H, Liu M, Yue Z, Wu Z, Liu L and Li F: Copper depletion strongly enhances ferroptosis via mitochondrial perturbation and reduction in antioxidative mechanisms. Antioxidants (Basel). 11:20842022. View Article : Google Scholar : PubMed/NCBI

Derseh HB, Perera KUE, Dewage SNV, Stent A, Koumoundouros E, Organ L, Pagel CN and Snibson KJ: Tetrathiomolybdate treatment attenuates bleomycin-induced angiogenesis and lung pathology in a sheep model of pulmonary fibrosis. Front Pharmacol. 12:7009022021. View Article : Google Scholar : PubMed/NCBI

Brewer GJ: The promise of copper lowering therapy with tetrathiomolybdate in the cure of cancer and in the treatment of inflammatory disease. J Trace Elem Med Biol. 28:372–378. 2014. View Article : Google Scholar : PubMed/NCBI

Zhang M, Qiu H, Mao L, Wang B, Li N, Fan Y, Weng P, Hu S, Dong X, Qin X, et al: Ammonium tetrathiomolybdate triggers autophagy-dependent NRF2 activation in vascular endothelial cells. Cell Death Dis. 13:7332022. View Article : Google Scholar : PubMed/NCBI

Wang T, Lu W, Cheng Z, Wang L, Jiang Z, Yue Y, Jiang P, Xia Z, He L, Wang F, et al: Oral engineered extracellular vesicles based on ion exchange strategy for multipronged management of Wilson's disease complicated with reproductive dysfunction therapy. Adv Sci (Weinh). 12:e016892025. View Article : Google Scholar : PubMed/NCBI

Ke Y, Wu C, Zeng Y, Chen M, Li Y, Xie C, Zhou Y, Zhong Y and Yu H: Radiosensitization of clioquinol combined with zinc in the nasopharyngeal cancer stem-like cells by inhibiting autophagy in vitro and in vivo. Int J Biol Sci. 16:777–789. 2020. View Article : Google Scholar : PubMed/NCBI

Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Yanase K, Namisaki T, Yamazaki M, Tsujinoue H, Imazu H and Fukui H: The copper-chelating agent, trientine, attenuates liver enzyme-altered preneoplastic lesions in rats by angiogenesis suppression. Oncol Rep. 10:1369–1373. 2003.PubMed/NCBI

Yang M, Wu X, Hu J, Wang Y, Wang Y, Zhang L, Huang W, Wang X, Li N, Liao L, et al: COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma. J Hepatol. 76:1138–1150. 2022. View Article : Google Scholar : PubMed/NCBI

Wang Y, Li W, Patel SS, Cong J, Zhang N, Sabbatino F, Liu X, Qi Y, Huang P, Lee H, et al: Blocking the formation of radiation-induced breast cancer stem cells. Oncotarget. 5:3743–3755. 2014. View Article : Google Scholar : PubMed/NCBI

Wu L, Meng F, Dong L, Block CJ, Mitchell AV, Wu J, Jang H, Chen W, Polin L, Yang Q, et al: Disulfiram and BKM120 in combination with chemotherapy impede tumor progression and delay tumor recurrence in tumor initiating cell-rich TNBC. Sci Rep. 9:2362019. View Article : Google Scholar : PubMed/NCBI

Sun T, Yang W, Toprani SM, Guo W, He L, DeLeo AB, Ferrone S, Zhang G, Wang E, Lin Z, et al: Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram. Cell Commun Signal. 18:362020. View Article : Google Scholar : PubMed/NCBI

Zhou P, Qin J, Zhou C, Wan G, Liu Y, Zhang M, Yang X, Zhang N and Wang Y: Multifunctional nanoparticles based on a polymeric copper chelator for combination treatment of metastatic breast cancer. Biomaterials. 195:86–99. 2019. View Article : Google Scholar : PubMed/NCBI

Hu H, Hua S, Lu F, Zhang W, Zhang Z, Cui J, Lei X, Xia J, Xu F and Zhou M: Mucous permeable nanoparticle for inducing cuproptosis-like death in broad-spectrum bacteria for nebulized treatment of acute pneumonia. Adv Sci (Weinh). 12:e24085802025. View Article : Google Scholar : PubMed/NCBI

Wu A, Yin N, Li Z, Zhang X, Zhang Z, Zhong T, Xia F, Pan J, Wang D, Liu L and Dong J: FDX1 facilitates elesclomol-induced cuproptosis and promotes glioblastoma development via transcription factor NFKB1. Biochem Pharmacol. 241:1171862025. View Article : Google Scholar : PubMed/NCBI

Wang W, Lu K, Jiang X, Wei Q, Zhu L, Wang X, Jin H and Feng L: Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer. J Exp Clin Cancer Res. 42:1422023. View Article : Google Scholar : PubMed/NCBI

Zulkifli M, Spelbring AN, Zhang Y, Soma S, Chen S, Li L, Le T, Shanbhag V, Petris MJ, Chen TY, et al: FDX1-dependent and independent mechanisms of elesclomol-mediated intracellular copper delivery. Proc Natl Acad Sci USA. 120:e22167221202023. View Article : Google Scholar : PubMed/NCBI

Chisholm CL, Wang H, Wong AH, Vazquez-Ortiz G, Chen W, Xu X and Deng CX: Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin. Oncotarget. 7:84439–84452. 2016. View Article : Google Scholar : PubMed/NCBI

Feng L, Wu TZ, Guo XR, Wang YJ, Wang XJ, Liu SX, Zhang R, Ma Y, Tan NH, Bian JL and Wang Z: Discovery of natural resorcylic acid lactones as novel potent copper ionophores covalently targeting PRDX1 to induce cuproptosis for triple-negative breast cancer therapy. ACS Cent Sci. 11:357–370. 2025. View Article : Google Scholar : PubMed/NCBI

Wen H, Qu C, Wang Z, Gao H, Liu W, Wang H, Sun H, Gu J, Yang Z and Wang X: Cuproptosis enhances docetaxel chemosensitivity by inhibiting autophagy via the DLAT/mTOR pathway in prostate cancer. FASEB J. 37:e231452023. View Article : Google Scholar : PubMed/NCBI

Ahire JJ, Neveling DP and Dicks LMT: Polyacrylonitrile (PAN) nanofibres spun with copper nanoparticles: An anti-Escherichia coli membrane for water treatment. Appl Microbiol Biotechnol. 102:7171–7181. 2018. View Article : Google Scholar : PubMed/NCBI

Cendrowska-Pinkosz M, Krauze M, Juśkiewicz J, Fotschki B and Ognik K: The influence of copper nanoparticles on neurometabolism marker levels in the brain and intestine in a rat model. Int J Mol Sci. 24:113212023. View Article : Google Scholar : PubMed/NCBI

Geng X, Liu K, Wang J, Su X, Shi Y and Zhao L: Preparation of ultra-small copper nanoparticles-loaded self-healing hydrogels with antibacterial, inflammation-suppressing and angiogenesis-enhancing properties for promoting diabetic wound healing. Int J Nanomedicine. 18:3339–3358. 2023. View Article : Google Scholar : PubMed/NCBI

Li L, Tai Z, Liu W, Luo Y, Wu Y, Lin S, Liu M, Gao B and Liu JX: Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis. iScience. 26:1064062023. View Article : Google Scholar : PubMed/NCBI

Petruzzelli R and Polishchuk RS: Activity and trafficking of copper-transporting ATPases in tumor development and defense against platinum-based drugs. Cells. 8:10802019. View Article : Google Scholar : PubMed/NCBI

Nayagam JS, Jeyaraj R, Foskett P, Dhawan A, Ala A, Joshi D, Bomford A and Thompson RJ: ATP7B genotype and chronic liver disease treatment outcomes in wilson disease: Worse survival with loss-of-function variants. Clin Gastroenterol Hepatol. 21:1323–1329.e4. 2023. View Article : Google Scholar

Wang Y, Li D, Xu K, Wang G and Zhang F: Copper homeostasis and neurodegenerative diseases. Neural Regen Res. 20:3124–3143. 2025. View Article : Google Scholar :

Chan N, Willis A, Kornhauser N, Ward MM, Lee SB, Nackos E, Seo BR, Chuang E, Cigler T, Moore A, et al: Influencing the tumor microenvironment: A phase II study of copper depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence and in preclinical models of lung metastases. Clin Cancer Res. 23:666–676. 2017. View Article : Google Scholar

Yang Z, Su W, Wei X, Pan Y, Xing M, Niu L, Feng B, Kong W, Ren X, Huang F, et al: Hypoxia inducible factor-1α drives cancer resistance to cuproptosis. Cancer Cell. 43:937–954.e9. 2025. View Article : Google Scholar

Zhang J, Han H, Wang L, Wang W, Yang M and Qin Y: Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment. Front Oncol. 12:9889562022. View Article : Google Scholar : PubMed/NCBI

Chen L, Ma S, Wu H, Zheng L, Yi Y, Liu G, Li B, Sun J, Du Y, Wang B, et al: Zonated copper-driven breast cancer progression countered by a copper-depleting nanoagent for immune and metabolic reprogramming. Adv Sci (Weinh). 12:e24124342025. View Article : Google Scholar : PubMed/NCBI