Disulfiram/copper shows potent cytotoxic effects on myelodysplastic syndromes via inducing Bip-mediated apoptosis and suppressing autophagy

Revised International Prognostic Scoring System for Myelodysplastic Syndromes

Greenberg, P. L., Tuechler, H., Schanz, J., Sanz, G. F., Garcia‐Manero, G., Solé, F. G., Bennett, J. M., Bowen, D., Fenaux, P., Dreyfus, F., et al. (2012) · Blood · doi:10.1182/blood-2012-03-420489 · Cited by 3,181 · see citing works

Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

Fenaux, P., Mufti, G. J., Hellstrom-Lindberg, E., Santini, V., Finelli, C., Giagounidis, A., Schoch, R., Gattermann, N., Sanz, G., List, A., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70003-8 · Cited by 2,663 · see citing works

Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress

Tabas, I. A., & Ron, D. (2011) · Nature Cell Biology · doi:10.1038/ncb0311-184 · Cited by 2,603 · see citing works

Targeting Autophagy in Cancer

Levy, J. M. M., Towers, C. G., & Thorburn, A. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.53 · Cited by 2,526 · see citing works

Mitochondria as multifaceted regulators of cell death

Bock, F. J., & Tait, S. W. G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0173-8 · Cited by 2,482 · see citing works

Deconvoluting the context-dependent role for autophagy in cancer

White, E. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3262 · Cited by 1,698 · see citing works

Protein misfolding in the endoplasmic reticulum as a conduit to human disease

Wang, M., & Kaufman, R. J. (2016) · Nature · doi:10.1038/nature17041 · Cited by 1,630 · see citing works

The Unfolded Protein Response and Cell Fate Control

Hetz, C. A., & Papa, F. R. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.06.017 · Cited by 1,567 · see citing works

The role for autophagy in cancer

White, E. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73941 · Cited by 1,332 · see citing works

The impact of the endoplasmic reticulum protein-folding environment on cancer development

Wang, M., & Kaufman, R. (2014) · Nature Reviews. Cancer · doi:10.1038/nrc3800 · Cited by 1,081 · see citing works

p62 at the crossroads of autophagy, apoptosis, and cancer

Moscat, J., & Diaz-Meco, M. T. (2009) · Cell · doi:10.1016/j.cell.2009.05.023 · Cited by 1,073 · see citing works

Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer

Cubillos-Ruiz, J., Bettigole, S., & Glimcher, L. (2017) · Cell · doi:10.1016/j.cell.2016.12.004 · Cited by 815 · see citing works

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4

Skrott, Z., Mistrik, M., Andersen, K. K., Friis, S., Majera, D., Gursky, J., Ozdian, T., Bartkova, J., Turi, Z., Moudry, P., et al. (2017) · Nature · doi:10.1038/nature25016 · Cited by 807 · see citing works

The Beclin 1–VPS34 complex – at the crossroads of autophagy and beyond

Funderburk, S. F., Wang, Q. J., & Yue, Z. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.03.002 · Cited by 778 · see citing works

Autophagy, Metabolism, and Cancer

White, E., Mehnert, J. M., & Chan, C. S. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0490 · Cited by 669 · see citing works

Autophagy Inhibition Compromises Degradation of Ubiquitin-Proteasome Pathway Substrates

Korolchuk, V. I., Mansilla, A., Menzies, F. M., & Rubinsztein, D. C. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.021 · Cited by 657 · see citing works

Further Analysis of Trials With Azacitidine in Patients With Myelodysplastic Syndrome: Studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B

Silverman, L. R., McKenzie, D. R., Peterson, B. L., Holland, J. F., Backstrom, J. T., Beach, C. L., & Larson, R. A. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.4346 · Cited by 550 · see citing works

The endoplasmic reticulum (ER) chaperone BiP is a master regulator of ER functions: Getting by with a little help from ERdj friends

Pobre, K. F. R., Poet, G. J., & Hendershot, L. M. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.rev118.002804 · Cited by 433 · see citing works

UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor

Kopp, M. C., Larburu, N., Durairaj, V., Adams, C. J., & Ali, M. M. U. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0324-9 · Cited by 417 · see citing works

Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine

Itzykson, R., Thépot, S., Quesnel, B., Dreyfus, F., Beyne‐Rauzy, O., Turlure, P., Vey, N., Récher, C., Dartigeas, C., Legros, L., et al. (2010) · Blood · doi:10.1182/blood-2010-06-289280 · Cited by 381 · see citing works

Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel

de Witte, T., Bowen, D., Robin, M., Malcovati, L., Niederwieser, D. W., Yakoub‐Agha, I., Mufti, G. J., Fenaux, P., Sanz, G. F., Martino, R., et al. (2017) · Blood · doi:10.1182/blood-2016-06-724500 · Cited by 381 · see citing works

Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS)

Malcovati, L., Porta, M. G. D., Strupp, C., Ambaglio, I., Kuendgen, A., Nachtkamp, K., Travaglino, E., Invernizzi, R., Pascutto, C., Lazzarino, M., et al. (2011) · Haematologica · doi:10.3324/haematol.2011.044602 · Cited by 282 · see citing works

Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy

Qian, X., Li, X., Cai, Q., Zhang, C., Yu, Q., Jiang, Y., Lee, J.-H., Hawke, D. H., Wang, Y., Xia, Y., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.01.027 · Cited by 281 · see citing works

BCL-2 family: integrating stress responses at the ER to control cell demise

Pihán, P., Carreras-Sureda, A., & Hetz, C. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.82 · Cited by 274 · see citing works

Disulfiram (DSF) acts as a copper ionophore to induce copper‐dependent oxidative stress and mediate anti‐tumor efficacy in inflammatory breast cancer

Allensworth, J. L., Evans, M. K., Bertucci, F., Aldrich, A. J., Festa, R. A., Finetti, P., Ueno, N. T., Safi, R., McDonnell, D. P., Thiele, D. J., et al. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2015.02.007 · Cited by 243 · see citing works

p62, an autophagy hero or culprit?

Rusten, T. E., & Stenmark, H. (2010) · Nature Cell Biology · doi:10.1038/ncb0310-207 · Cited by 237 · see citing works

Ni(II), Cu(II), and Zn(II) Diethyldithiocarbamate Complexes Show Various Activities Against the Proteasome in Breast Cancer Cells

Cvek, B., Milacic, V., Taraba, J., & Dou, Q. P. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8007807 · Cited by 208 · see citing works

The combination of disulfiram and copper for cancer treatment

Li, H., Wang, J., Wu, C., Wang, L., Chen, Z.-S., & Cui, W. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.04.003 · Cited by 185 · see citing works

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

Jabbour, E. J., Short, N. J., Bravo, G. M., Huang, X., Bueso-Ramos, C., Qiao, W., Yang, H., Zhao, C., Kadia, T. M., Borthakur, G. M., et al. (2017) · Blood · doi:10.1182/blood-2017-06-788497 · Cited by 183 · see citing works

Clinical Implications of Genetic Mutations in Myelodysplastic Syndrome

Kennedy, J. A., & Ebert, B. L. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.0806 · Cited by 170 · see citing works

Clonal evolution in myelodysplastic syndromes

da Silva-Coelho, P., Kroeze, L. I., Yoshida, K., Koorenhof‐Scheele, T. N., Knops, R., van de Locht, L. T., de Graaf, A. O., Massop, M., Sandmann, S., Dugas, M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15099 · Cited by 150 · see citing works

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

Xu, B., Wang, S., Li, R., Chen, K., He, L., Deng, M., Kannappan, V., Zha, J., Dong, H., & Wang, W. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.176 · Cited by 141 · see citing works

Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM)

Porta, M. G. D., Tuechler, H., Malcovati, L., Schanz, J., Sanz, G. F., Garcia‐Manero, G., Solé, F. G., Bennett, J. M., Bowen, D., Fenaux, P., et al. (2015) · Leukemia · doi:10.1038/leu.2015.55 · Cited by 134 · see citing works

MITOL prevents ER stress‐induced apoptosis by IRE1α ubiquitylation at ER–mitochondria contact sites

Takeda, K., Nagashima, S., Shiiba, I., Uda, A., Tokuyama, T., Ito, N., Fukuda, T., Matsushita, N., Ishido, S., Iwawaki, T., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100999 · Cited by 123 · see citing works

Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents

Ekinci, E., Rohondia, S. O., Khan, R., & Dou, Q. P. (2019) · Recent Patents on Anti-Cancer Drug Discovery · doi:10.2174/1574892814666190514104035 · Cited by 119 · see citing works

The unfolded protein response as a target for anticancer therapeutics

Wang, M., Law, M. E., Castellano, R. K., & Law, B. K. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.05.003 · Cited by 118 · see citing works

Nonprofit drugs as the salvation of the world's healthcare systems: the case of Antabuse (disulfiram)

Cvek, B. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.12.010 · Cited by 115 · see citing works

Mining for therapeutic gold

Collins, F. S. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3461 · Cited by 108 · see citing works

Disulfiram targeting lymphoid malignant cell lines via ROS-JNK activation as well as Nrf2 and NF-kB pathway inhibition

Zha, J., Chen, F., Dong, H., Shi, P., Yao, Y., Zhang, Y., Li, R., Wang, S., Li, P., Wang, W., et al. (2014) · Journal of Translational Medicine · doi:10.1186/1479-5876-12-163 · Cited by 108 · see citing works

BH3‐only proteins are part of a regulatory network that control the sustained signalling of the unfolded protein response sensor IRE1α

Rodríguez, D. A., Zamorano, S., Lisbona, F., Rojas‐Rivera, D., Urra, H., Cubillos‐Ruiz, J. R., Armisén, R., Henríquez, D. R., Cheng, E. H. Y., Letek, M., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.84 · Cited by 107 · see citing works

Akt is the downstream target of GRP78 in mediating cisplatin resistance in ER stress-tolerant human lung cancer cells

Lin, Y., Wang, Z., Liu, L., & Chen, L. (2010) · Lung Cancer · doi:10.1016/j.lungcan.2010.06.004 · Cited by 87 · see citing works

Suppressing autophagy enhances disulfiram/copper-induced apoptosis in non-small cell lung cancer

Wu, X., Xue, X., Wang, L., Wang, W., Han, J., Sun, X., Zhang, H., Liu, Y., Che, X., Yang, J., et al. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.02.039 · Cited by 78 · see citing works

Targeting Cancer Cells via the Reactive Oxygen Species-Mediated Unfolded Protein Response with a Novel Synthetic Polyphenol Conjugate

Shin, S. Y., Lee, J. M., Lee, M. S., Koh, D., Jung, H., Lim, Y., & Lee, Y. H. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0424 · Cited by 62 · see citing works

Azacitidine in the ‘real‐world’: an evaluation of 1101 higher‐risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada

Mozessohn, L., Cheung, M. C., Fallahpour, S., Gill, T., Maloul, A., Zhang, L., Lau, O., & Buckstein, R. J. (2018) · British Journal of Haematology · doi:10.1111/bjh.15273 · Cited by 58 · see citing works

Anti-cancer effects of disulfiram in head and neck squamous cell carcinoma via autophagic cell death

Park, Y. M., Go, Y. Y., Shin, S. H., Cho, J., Woo, J., & Song, J. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203069 · Cited by 49 · see citing works

Targeting the NPL4 Adaptor of p97/VCP Segregase by Disulfiram as an Emerging Cancer Vulnerability Evokes Replication Stress and DNA Damage while Silencing the ATR Pathway

Majera, D., Skrott, Z., Chroma, K., Merchut-Maya, J. M., Mistrik, M., & Bartek, J. (2020) · Cells · doi:10.3390/cells9020469 · Cited by 43 · see citing works

Therapeutic strategies in low and high-risk MDS: What does the future have to offer?

Scalzulli, E., Pepe, S., Colafigli, G., & Breccia, M. (2020) · Blood Reviews · doi:10.1016/j.blre.2020.100689 · Cited by 36 · see citing works

Disulfiram with or without metformin inhibits oesophageal squamous cell carcinoma in vivo

Jivan, R., Peres, J., Damelin, L. H., Wadee, R., Veale, R. B., Prince, S., & Mavri‐Damelin, D. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.12.026 · Cited by 34 · see citing works

Lack of cross‐resistance to FF‐10501, an inhibitor of inosine‐5′‐monophosphate dehydrogenase, in azacitidine‐resistant cell lines selected from SKM‐1 and MOLM‐13 leukemia cell lines

Murase, M., IWAMURA, H., Komatsu, K., Saito, M., Maekawa, T., Nakamura, T., Yokokawa, T., & Shimada, Y. (2016) · Pharmacology Research & Perspectives · doi:10.1002/prp2.206 · Cited by 19 · see citing works

Synergistic Effect and Molecular Mechanism of Homoharringtonine and Bortezomib on SKM-1 Cell Apoptosis

Zhang, J., Chen, B., Wu, T., Wang, Q., Zhuang, L., Zhu, C. Y., Fan, N., Qing, W., Ma, Y., & Xu, X. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142422 · Cited by 10 · see citing works

Recent Advances in Cancer Therapeutic Copper-Based Nanomaterials for Antitumor Therapy

Aishajiang, R., Liu, Z., Wang, T., Zhou, L. Y., & Yu, D. N. (2023) · Molecules · doi:10.3390/molecules28052303 · Cited by 95 · see citing works

Copper-Based biomaterials for anti-tumor therapy: Recent advances and perspectives

Zhang, S., & Peng, S. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.01.014 · Cited by 56 · see citing works

Inducers of Autophagy and Cell Death: Focus on Copper Metabolism

Ling, W., Li, S., Zhu, Y., Wang, X., Jiang, D., & Kang, B. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.117725 · Cited by 37 · see citing works

Application of Disulfiram and its Metabolites in Treatment of Inflammatory Disorders

Guo, W., Chen, S., Li, C., Xu, J., & Wang, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.795078 · Cited by 37 · see citing works

Copper Nanoparticles Green-Formulated by Curcuma longa Extract Induce Apoptosis via P53 and STAT3 Signaling Pathways in Bladder Carcinoma Cell

Xing, T., Wang, Z., Hao, X., Mu, J., & Wang, B. (2024) · Biological Trace Element Research · doi:10.1007/s12011-024-04373-4 · Cited by 12 · see citing works

Involvement of copper in cell death and cancer

Xie, J., Su, Y., Shang, W., Wu, Y., He, J., Li, T., Shen, Y., Zhang, Y.-N., Tong, X., & Bian, Q. (2024) · APOPTOSIS · doi:10.1007/s10495-024-02059-9 · Cited by 12 · see citing works

Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma

Zhong, M., Tan, J., Pan, G., Jiang, Y., Zhou, H., Lai, Q., Chen, Q., Fan, L., Deng, M., Xu, B., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.780118 · Cited by 9 · see citing works

Mechanisms of Copper-Induced Autophagy and Links with Human Diseases

Fu, Y., Zeng, S., Wang, Z., Huang, H., Zhao, X., & Li, M. (2025) · Pharmaceuticals · doi:10.3390/ph18010099 · Cited by 8 · see citing works

Cuproptosis and its cooperative role in cancer therapy: exploring new treatment strategies

Xu, Q., Lai, Q., Wang, J., Feng, S., Gu, W., Song, L., Wang, S., Xiao, Y., & Zhao, Q. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2025.217519 · Cited by 7 · see citing works

Decoration of copper nanoparticles (Cu2O NPs) over chitosan-guar gum: Its application in the Sonogashira cross-coupling reactions and treatment of human lung adenocarcinoma

Cheng, X., Hemmati, S., Pirhayati, M., Zangeneh, M. M., & Veisi, H. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.141122 · Cited by 6 · see citing works

Characterization, cytotoxicity and anti-human renal cell carcinoma efficacies of copper nanoparticles green-synthesized by Panax ginseng

Meng, F., & Li, Z. (2024) · Inorganic Chemistry Communications · doi:10.1016/j.inoche.2024.112263 · Cited by 5 · see citing works

New insights into the regulation of Cystathionine beta synthase (CBS), an enzyme involved in intellectual deficiency in Down syndrome

Conan, P., Léon, A., Caroff, N., Rollet, C., Chaïr, L., Martin, J., Bihel, F. J. ‐., Mignen, O., Voisset, C., & Friocourt, G. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1110163 · Cited by 5 · see citing works

Research progress on ferroptosis in Myelodysplastic syndromes

Yang, Y., Han, J., Wei, Y., Jin, J., & Feng, W. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1561072 · Cited by 3 · see citing works

Preparation, Characterization, and Determination of the Cytotoxicity, Antioxidant, and Anti–Lung Cancer Properties of Plant Leaf Extract Green‐Synthesized Nanoparticles

Li, Y., Wang, F., & An, X. (2025) · Applied Organometallic Chemistry · doi:10.1002/aoc.70255 · Cited by 2 · see citing works

Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence

Benkő, B.-M., De Brito Parreirinha, N. S., Sebe, I., & Zelkó, R. (2026) · iScience · doi:10.1016/j.isci.2026.115441 · Cited by 2 · see citing works

Syzygium aromaticum leaf extract promoted biogenic CuO nanoparticles for the anti-apoptotic efficacies of NCI-H661 human lung adenocarcinoma cell line and following the PI3K/AKT/mTOR signaling pathway

Nian, F., Xue, M., Zhou, W., & Zhang, S. (2026) · 3 Biotech · doi:10.1007/s13205-025-04633-7 · Cited by 1 · see citing works

[The advancement of cuproptosis in hematological tumors].

Zhou, L. J., Li, Y. Y., Zhang, L. Y., & Zhang, J. (2024) · PubMed Central · doi:10.3760/cma.j.cn121090-20240327-00116

Pro-apoptotic and Anti-breast Cancer Activities of Copper Nanoparticles on MCF-7 Cells and their Effect on the PI3K/AKT/mTOR Signalling Pathway

Zhou, B., Li, W., Li, S., & Zhou, Z. (2026) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-026-10456-7

Disulfiram, an old drug with new potential therapeutic uses for human hematological malignancies

Conticello, C., Martinetti, D., Adamo, L., Buccheri, S., Giuffrida, R., Parrinello, N. L., Lombardo, L., Anastasi, G., Amato, G., Cavalli, M. M., et al. (2012) · International Journal of Cancer · doi:10.1002/ijc.27482 · Cited by 86 · see citing works

Disulfiram/copper markedly induced myeloma cell apoptosis through activation of JNK and intrinsic and extrinsic apoptosis pathways

Xu, Y., Zhou, Q., Feng, X., Dai, Y., Jiang, Y. Z., Jiang, W., Liu, X., Xing, X., Wang, Y., Ni, Y., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110048 · Cited by 55 · see citing works

Disulfiram/copper causes ROS levels alteration, cell cycle inhibition, and apoptosis in acute myeloid leukaemia cell lines with modulation in the expression of related genes

Hassani, S., Ghaffari, P., Chahardouli, B., Alimoghaddam, K., Ghavamzadeh, A., Alizadeh, S., & Ghaffari, S. H. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.01.109 · Cited by 86 · see citing works

Disulfiram, an clinically used anti-alcoholism drug has the potential to target acute myeloid leukemia cells in a copper-dependent manner in vivo

Xu, B., Li, R., Dong, H., Chen, F., Liu, Y., Wang, S., & Zhou, S.-Y. (2013) · Blood · doi:10.1182/blood.v122.21.5040.5040

Disulfiram Combined with Copper Induces Acute Myeloid Leukemic Stem-like KG1a Cell Apoptosis through TNF-a/ROS Pathway

Xu, B., Zhou, Y., Deng, M., Zhong, W., Chen, K., Dong, H., Yan, D., & Zhou, S.-Y. (2015) · Blood · doi:10.1182/blood.v126.23.4923.4923 · Cited by 1 · see citing works