{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T10:53:38Z","timestamp":1793012018891,"version":"4.5.0"},"reference-count":236,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T00:00:00Z","timestamp":1601856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Organometallics, such as copper compounds, are cancer chemotherapeutics used alone or in combination with other drugs. One small group of copper complexes exerts an effective inhibitory action on topoisomerases, which participate in the regulation of DNA topology. Copper complexes inhibitors of topoisomerases 1 and 2 work by different molecular mechanisms, analyzed herein. They allow genesis of DNA breaks after the formation of a ternary complex, or act in a catalytic mode, often display DNA intercalative properties and ROS production, and sometimes display dual effects. These amplified actions have repercussions on the cell cycle checkpoints and death effectors. Copper complexes of topoisomerase inhibitors are analyzed in a broader synthetic view and in the context of cancer cell mutations. Finally, new emerging treatment aspects are depicted to encourage the expansion of this family of highly active anticancer drugs and to expend their use in clinical trials and future cancer therapy.<\/jats:p>","DOI":"10.3390\/cancers12102863","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T08:35:57Z","timestamp":1601886957000},"page":"2863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":194,"title":["Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7002-5030","authenticated-orcid":false,"given":"Caroline","family":"Molinaro","sequence":"first","affiliation":[{"name":"Univ. Lille, CNRS, UMR 8576-UGSF-Unit\u00e9 de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5684-1728","authenticated-orcid":false,"given":"Alain","family":"Martoriati","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, UMR 8576-UGSF-Unit\u00e9 de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydie","family":"Pelinski","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Centrale Lille, Univ. Artois, UMR 8181-UCCS-Unit\u00e9 de Catalyse et Chimie du Solide, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1772-1034","authenticated-orcid":false,"given":"Katia","family":"Cailliau","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, UMR 8576-UGSF-Unit\u00e9 de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/222385a0","article-title":"Platinum compounds: A new class of potent antitumour agents","volume":"222","author":"Rosenberg","year":"1969","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1021\/ed083p728","article-title":"The discovery and development of cisplatin","volume":"83","author":"Alderden","year":"2006","journal-title":"J. Chem. Educ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s00280-016-2976-z","article-title":"Platinum-based drugs: Past, present and future","volume":"77","author":"Dilruba","year":"2016","journal-title":"Cancer Chemother. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ccr.2018.01.009","article-title":"The mechanism of tumour cell death by metal-based anticancer drugs is not only a matter of DNA interactions","volume":"360","author":"Bergamo","year":"2018","journal-title":"Coord. Chem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: Molecular mechanisms of action","volume":"740","author":"Dasari","year":"2014","journal-title":"Eur. J. Pharm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s40620-017-0392-z","article-title":"Cisplatin nephrotoxicity: A review of the literature","volume":"31","author":"Manohar","year":"2018","journal-title":"J. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3389\/fphar.2017.00196","article-title":"characterization of cardiovascular alterations induced by different chronic cisplatin treatments","volume":"8","author":"Uranga","year":"2017","journal-title":"Front. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1124\/pr.111.005637","article-title":"Cisplatin resistance: A cellular self-defense mechanism resulting from multiple epigenetic and genetic changes","volume":"64","author":"Shen","year":"2012","journal-title":"Pharm. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chen, S.H., and Chang, J.Y. (2019). New insights into mechanisms of cisplatin resistance: From tumor cell to microenvironment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174136"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e98597","DOI":"10.15252\/embj.201798597","article-title":"Metabolic vulnerability of cisplatin-resistant cancers","volume":"37","author":"Obrist","year":"2018","journal-title":"EMBO J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.phrs.2016.01.001","article-title":"Cisplatin resistance and opportunities for precision medicine","volume":"106","author":"Amable","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/onc.2011.384","article-title":"Molecular mechanisms of cisplatin resistance","volume":"31","author":"Galluzzi","year":"2012","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., and Sarkar, S. (2014). Drug resistance in cancer: An overview. Cancers, 6.","DOI":"10.3390\/cancers6031769"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.3389\/fphys.2018.01898","article-title":"Cisplatin-membrane interactions and their influence on platinum complexes activity and toxicity","volume":"9","author":"Martinho","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.1039\/C7CS00195A","article-title":"The development of anticancer ruthenium(ii) complexes: From single molecule compounds to nanomaterials","volume":"46","author":"Zeng","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jorganchem.2017.03.038","article-title":"Advances in the design of organometallic anticancer complexes","volume":"839","author":"Zhang","year":"2017","journal-title":"J. Org. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8802","DOI":"10.1039\/C5CS00486A","article-title":"Ferrocifen type anti cancer drugs","volume":"44","author":"Jaouen","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7588","DOI":"10.1039\/b905798f","article-title":"A categorization of metal anticancer compounds based on their mode of action","volume":"37","author":"Gianferrara","year":"2009","journal-title":"Dalton Trans."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1039\/B707077M","article-title":"Bioorganometallic chemistry from teaching paradigms to medicinal applications","volume":"38","author":"Hartinger","year":"2009","journal-title":"Chem. Soc. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1021\/acs.organomet.6b00440","article-title":"Synthesis, structure, and antiproliferative activity of ruthenium(ii) arene complexes of indenoisoquinoline derivatives","volume":"35","author":"Wambang","year":"2016","journal-title":"Organometallics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.bmc.2015.12.033","article-title":"Synthesis and biological activity of ferrocenyl indeno[1,2-c]isoquinolines as topoisomerase II inhibitors","volume":"24","author":"Wambang","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2174\/156802612799078964","article-title":"Next-generation anticancer metallodrug","volume":"12","author":"Komeda","year":"2012","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_23","first-page":"213","article-title":"Mechanism of action of anticancer metallodrugs","volume":"Volume 10","author":"Rai","year":"2018","journal-title":"Biomedical Applications of Metals"},{"key":"ref_24","first-page":"469","article-title":"Copper complexes in cancer therapy","volume":"18","author":"Denoyer","year":"2018","journal-title":"Met. Ions Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/cr400135x","article-title":"Advances in copper complexes as anticancer agents","volume":"114","author":"Santini","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1089\/ars.2010.3663","article-title":"Anticancer activity of metal complexes: Involvement of redox processes","volume":"15","author":"Jungwirth","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.2174\/092986709787846532","article-title":"Copper compounds in anticancer strategies","volume":"16","author":"Tardito","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2174\/187152009787313837","article-title":"Copper complexes as anticancer agents","volume":"9","author":"Marzano","year":"2009","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_29","first-page":"91","article-title":"Recent advances in anticancer copper compounds","volume":"Volume 14","author":"Vessieres","year":"2019","journal-title":"Metal-Based Anticancer Agents"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s10534-014-9736-5","article-title":"The many \u201cfaces\u201d of copper in medicine and treatment","volume":"27","author":"Hordyjewska","year":"2014","journal-title":"Biometals"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000438485","article-title":"Behind the link between copper and angiogenesis: Established mechanisms and an overview on the role of vascular copper transport systems","volume":"52","author":"Urso","year":"2015","journal-title":"J. Vasc. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10911-006-9003-7","article-title":"The role of copper in tumour angiogenesis","volume":"10","author":"Lowndes","year":"2005","journal-title":"J. Mammary Gland. Biol. Neoplasia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/(SICI)1097-4644(19980601)69:3<326::AID-JCB10>3.0.CO;2-A","article-title":"Copper stimulates proliferation of human endothelial cells under culture","volume":"69","author":"Hu","year":"1998","journal-title":"J. Cell. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/BF01324697","article-title":"Quantitative analysis of copper, zinc and copper\/zinc ratio in selected human brain tumors","volume":"16","author":"Yoshida","year":"1993","journal-title":"J. Neurooncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1088\/0031-9155\/47\/13\/310","article-title":"Concentrations of Fe, Cu and Zn in breast tissue: A synchrotron XRF study","volume":"47","author":"Geraki","year":"2002","journal-title":"Phys. Med. Biol."},{"key":"ref_36","first-page":"108","article-title":"Copper and ceruloplasmin status in serum of prostate and colon cancer patients","volume":"47","author":"Nayak","year":"2003","journal-title":"Indian J. Physiol. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000226722","article-title":"Serum and tissue trace metal levels in lung cancer","volume":"46","author":"Arroyo","year":"1989","journal-title":"Oncology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.ejim.2012.07.009","article-title":"Copper levels in patients with hematological malignancies","volume":"23","author":"Kaiafa","year":"2012","journal-title":"Eur. J. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Baldari, S., Di Rocco, G., and Toietta, G. (2020). Current biomedical use of copper chelation therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031069"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1039\/C5MT00149H","article-title":"Targeting copper in cancer therapy: \u2018Copper That Cancer\u2019","volume":"7","author":"Denoyer","year":"2015","journal-title":"Metallomics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1021\/cb400198p","article-title":"Increasing intracellular bioavailable copper selectively targets prostate cancer cells","volume":"8","author":"Cater","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1042\/BJ20110123","article-title":"Clioquinol induces cytoplasmic clearance of the X-linked inhibitor of apoptosis protein (XIAP): Therapeutic indication for prostate cancer","volume":"436","author":"Cater","year":"2011","journal-title":"Biochem. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cheriyan, V.T., Wang, Y., Muthu, M., Jamal, S., Chen, D., Yang, H., Polin, L.A., Tarca, A.L., Pass, H.I., and Dou, Q.P. (2014). Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093711"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.bbrc.2014.03.047","article-title":"Inhibitory effect of Disulfiram\/copper complex on non-small cell lung cancer cells","volume":"446","author":"Duan","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1002\/jcb.25184","article-title":"Disulfiram\/copper-disulfiram damages multiple protein degradation and turnover pathways and cytotoxicity is enhanced by metformin in oesophageal squamous cell carcinoma cell lines","volume":"116","author":"Jivan","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5819","DOI":"10.1158\/0008-5472.CAN-13-3527","article-title":"Copper signaling axis as a target for prostate cancer therapeutics","volume":"74","author":"Safi","year":"2014","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.2174\/092986710791859315","article-title":"Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry","volume":"17","author":"Wang","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3892\/mmr.2016.6022","article-title":"Novel copper complexes as potential proteasome inhibitors for cancer treatment","volume":"15","author":"Zhang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Krasnovskaya, O., Naumov, A., Guk, D., Gorelkin, P., Erofeev, A., Beloglazkina, E., and Majouga, A. (2020). Copper Coordination Compounds as Biologically Active Agents. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113965"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1002\/ejic.201500175","article-title":"Possible DNA-interacting pathways for metal-based compounds exemplified with copper coordination compounds","volume":"16","author":"Brissos","year":"2015","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"20175","DOI":"10.1016\/S0021-9258(18)54906-1","article-title":"Covalent modification of guanine bases in double-stranded DNA","volume":"266","author":"Kagawa","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"126905","DOI":"10.1016\/j.bmcl.2019.126905","article-title":"From coins to cancer therapy: Gold, silver and copper complexes targeting human topoisomerases","volume":"30","author":"Ceramella","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s10895-018-2283-7","article-title":"Recent advances in copper intercalators as anticancer agents","volume":"28","author":"Thulasiram","year":"2018","journal-title":"J. Fluoresc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ejmech.2019.03.034","article-title":"A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade","volume":"171","author":"Liang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00280-017-3334-5","article-title":"DNA topoisomerase-targeting chemotherapeutics: What\u2019s new?","volume":"80","author":"Cuya","year":"2017","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1158\/1078-0432.CCR-19-1089","article-title":"Targeting topoisomerase I in the era of precision medicine","volume":"25","author":"Thomas","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1021\/cb300648v","article-title":"Drugging topoisomerases: Lessons and challenges","volume":"8","author":"Pommier","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bjornsti, M.A., and Kaufmann, S.H. (2019). Topoisomerases and cancer chemotherapy: Recent advances and unanswered questions. F1000 Res., 8.","DOI":"10.12688\/f1000research.20201.1"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nrm.2016.111","article-title":"Roles of eukaryotic topoisomerases in transcription, replication and genomic stability","volume":"17","author":"Pommier","year":"2016","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.chembiol.2010.04.012","article-title":"DNA topoisomerases and their poisoning by anticancer and antibacterial drugs","volume":"17","author":"Pommier","year":"2010","journal-title":"Chem. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.apsb.2018.07.008","article-title":"Recent developments in topoisomerase-targeted cancer chemotherapy","volume":"8","author":"Hevener","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Xu, Y., and Her, C. (2015). Inhibition of Topoisomerase (DNA) I (TOP1): DNA damage repair and anticancer therapy. Biomolecules, 5.","DOI":"10.3390\/biom5031652"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/0022-2836(71)90334-2","article-title":"Interaction between DNA and an Escherichia coli protein omega","volume":"55","author":"Wang","year":"1971","journal-title":"J. Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Madabhushi, R. (2018). The roles of DNA topoisomerase II\u03b2 in transcription. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071917"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1266\/ggs.15-00023","article-title":"The distinctive cellular responses to DNA strand breaks caused by a DNA topoisomerase I poison in conjunction with DNA replication and RNA transcription","volume":"90","author":"Sakasai","year":"2016","journal-title":"Genes Genet. Syst."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lee, J.H., and Berger, J.M. (2019). Cell cycle-dependent control and roles of DNA topoisomerase II. Genes, 10.","DOI":"10.3390\/genes10110859"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.gpb.2016.02.004","article-title":"Topoisomerase I in human disease pathogenesis and treatments","volume":"14","author":"Li","year":"2016","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0163-7258(03)00058-5","article-title":"Catalytic topoisomerase II inhibitors in cancer therapy","volume":"99","author":"Larsen","year":"2003","journal-title":"Pharm. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8947","DOI":"10.1021\/acs.jmedchem.7b01202","article-title":"Discovery of novel topoisomerase II inhibitors by medicinal chemistry approaches","volume":"61","author":"Hu","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jinorgbio.2018.05.012","article-title":"Comparative studies of oxindolimine-metal complexes as inhibitors of human DNA topoisomerase IB","volume":"186","author":"Castelli","year":"2018","journal-title":"J. Inorg. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1039\/C3MT00099K","article-title":"Effect of oxindolimine copper(ii) and zinc(ii) complexes on human topoisomerase I activity","volume":"6","author":"Katkar","year":"2014","journal-title":"Metallomics"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.jinorgbio.2005.03.013","article-title":"Isatin-Schiff base copper(II) complexes and their influence on cellular viability","volume":"99","author":"Cerchiaro","year":"2005","journal-title":"J. Inorg. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"12010","DOI":"10.1074\/jbc.M610927200","article-title":"Pro-apoptotic activity of novel Isatin-Schiff base copper(II) complexes depends on oxidative stress induction and organelle-selective damage","volume":"282","author":"Filomeni","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ejmech.2014.02.049","article-title":"Copper complexes with phosphonium containing hydrazone ligand: Topoisomerase inhibition and cytotoxicity study","volume":"76","author":"Chew","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"10824","DOI":"10.1039\/b910133k","article-title":"Cytotoxicity of the traditional chinese medicine (tcm) plumbagin in its copper chemistry","volume":"48","author":"Chen","year":"2009","journal-title":"Dalton Trans."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s10534-012-9572-4","article-title":"Biological and cytoselective anticancer properties of copper(II)-polypyridyl complexes modulated by auxiliary methylated glycine ligand","volume":"25","author":"Seng","year":"2012","journal-title":"BioMetals"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.jinorgbio.2009.07.010","article-title":"Pyrophosphate-bridged complexes with picomolar toxicity","volume":"103","author":"Ikotun","year":"2009","journal-title":"J. Inorg. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jphotobiol.2012.05.017","article-title":"Synthesis of heterobimetallic complexes: In vitro DNA binding, cleavage and antimicrobial studies","volume":"114","author":"Tabassum","year":"2012","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1021\/ic061753a","article-title":"DNA binding studies of novel copper(ii) complexes containing l-tryptophan as chiral auxiliary:\u2009in vitro antitumor activity of cu\u2212sn2 complex in human neuroblastoma cells","volume":"46","author":"Chauhan","year":"2007","journal-title":"Inorg. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1080\/07391102.2018.1459321","article-title":"Carbohydrate-based heteronuclear complexes as topoisomerase I\u03b1 inhibitor: Approach toward anticancer chemotherapeutics","volume":"37","author":"Afzal","year":"2019","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"16749","DOI":"10.1039\/c3dt51209f","article-title":"Chiral heterobimetallic complexes targeting human DNA-topoisomerase I\u03b1","volume":"42","author":"Tabassum","year":"2013","journal-title":"Dalton Trans."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"47439","DOI":"10.1039\/C5RA07333B","article-title":"A multifunctional molecular entity CuII\u2013SnIV heterobimetallic complex as a potential cancer chemotherapeutic agent: DNA binding\/cleavage, SOD mimetic, topoisomerase Ia inhibitory and in vitrocytotoxic activities","volume":"5","author":"Tabassum","year":"2015","journal-title":"RSC Adv."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"60280","DOI":"10.1039\/C4RA09256B","article-title":"Zinc, copper and nickel derivatives of 2-[2-bromoethyliminomethyl]phenol as topoisomerase inhibitors exhibiting anti-proliferative and antimetastatic properties","volume":"4","author":"Lee","year":"2014","journal-title":"RSC Adv."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jinorgbio.2016.02.010","article-title":"Topoisomerase I inhibition and DNA cleavage by zinc, copper, and nickel derivatives of 2-[2-bromoethyliminomethyl]-4-[ethoxymethyl]phenol complexes exhibiting anti-proliferation and anti-metastasis activity","volume":"159","author":"Lee","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.abb.2016.07.009","article-title":"Human topoisomerase IB is a target of a thiosemicarbazone copper(II) complex","volume":"606","author":"Vutey","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1080\/24701556.2019.1571514","article-title":"Tetrazolo[1,5-a]pyrimidine-based metal(II) complexes as therapeutic agents: DNA interaction, targeting topoisomerase I and cyclin-dependent kinase studies","volume":"48","author":"Haleel","year":"2019","journal-title":"Inorg. Nano Met. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.msec.2016.05.120","article-title":"Antioxidant, DNA interaction, VEGFR2 kinase, topoisomerase I and in vitro cytotoxic activities of heteroleptic copper(II) complexes of tetrazolo[1,5-a]pyrimidines and diimines","volume":"68","author":"Haleel","year":"2016","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1039\/c2dt12044e","article-title":"Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor","volume":"41","author":"Tabassum","year":"2012","journal-title":"Dalton Trans."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.bcp.2014.12.008","article-title":"Cellular mechanisms of the cytotoxicity of the anticancer drug elesclomol and its complex with Cu(II)","volume":"93","author":"Hasinoff","year":"2015","journal-title":"Biochem. Pharm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"18359","DOI":"10.1039\/C9RA03130H","article-title":"Induction of cell cycle arrest and apoptosis by copper complex Cu(SBCM)2 towards oestrogen-receptor positive MCF-7 breast cancer cells","volume":"9","author":"Foo","year":"2019","journal-title":"RSC Adv."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s10534-018-0096-4","article-title":"Copper complex derived fromS-benzyldithiocarbazate and 3-acetylcoumarin induced apoptosis in breast cancer cell","volume":"4","author":"Foo","year":"2018","journal-title":"Biometals"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1053\/j.seminoncol.2019.10.006","article-title":"Mechanisms and clinical course of cardiovascular toxicity of cancer treatment I. Oncology","volume":"46","author":"Yeh","year":"2019","journal-title":"Semin. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/nyas.12358","article-title":"Topoisomerase II and leukemia","volume":"1310","author":"Pendleton","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/BF00143498","article-title":"Copper(II) complexes of 6-methyl-2-acetylpyridine N(4)-substituted thiosemicarbazones","volume":"20","author":"West","year":"1995","journal-title":"Trans. Met. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/(SICI)1521-4184(199804)331:4<121::AID-ARDP121>3.0.CO;2-T","article-title":"The Cytotoxicity of 2-Formyl and 2-Acetyl-(6-picolyl)-4 N-Substituted Thiosemicarbazones and Their Copper(II) Complexes","volume":"331","author":"Miller","year":"1998","journal-title":"Arch. Pharm. Pharm. Med. Chem."},{"key":"ref_96","first-page":"1","article-title":"Anticancer potential of metal thiosemicarbazone complexes: A review","volume":"6","author":"Khan","year":"2015","journal-title":"Chem. Sin."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1021\/jm9014394","article-title":"A series of \u03b1-heterocyclic carboxaldehyde thiosemicarbazones inhibit topoisomerase II\u03b1 catalytic activity","volume":"53","author":"Huang","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"146","DOI":"10.4236\/ojic.2016.62010","article-title":"Cu(II) benzoylpyridine thiosemicarbazone complexes: Inhibition of human topoisomerase II\u03b1 and activity against breast cancer cells","volume":"6","author":"Conner","year":"2016","journal-title":"Open J. Inorg. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1021\/acs.chemrestox.5b00471","article-title":"Examination of the impact of copper(ii) \u03b1-(n)-heterocyclic thiosemicarbazone complexes on dna topoisomerase II\u03b1","volume":"29","author":"Wilson","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1021\/acs.chemrestox.9b00311","article-title":"Clarifying the mechanism of copper(II) \u03b1-(N)-heterocyclic thiosemicarbazone complexes on DNA topoisomerase II\u03b1 and II\u03b2","volume":"32","author":"Keck","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/(SICI)1099-0739(199901)13:1<9::AID-AOC818>3.0.CO;2-#","article-title":"Multiple Mechanisms for Cytotoxicity Induced by Copper(II) Complexes of 2-Acetylpyrazine-N-substituted Thiosemicarbazones","volume":"13","author":"Miller","year":"1999","journal-title":"Appl. Organometal. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1021\/jm101532u","article-title":"Role of metalation in the topoisomerase II\u03b1 inhibition and antiproliferation activity of a series of \u03b1-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes","volume":"54","author":"Zeglis","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_103","first-page":"30","article-title":"Cu(II) propionyl-thiazole thiosemicarbazone complexes: Crystal structure, inhibition of human topoisomerase II\u03b1, and activity against breast cancer cells","volume":"8","author":"Lisic","year":"2018","journal-title":"Open J. Med. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1021\/acs.chemrestox.8b00204","article-title":"Structural and metal ion effects on human topoisomerase II\u03b1 inhibition by \u03b1-(N)-heterocyclic thiosemicarbazones","volume":"32","author":"Morris","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.inoche.2015.12.013","article-title":"A novel copper(II) complex identified as a potent drug against colorectal and breast cancer cells and as a poison inhibitor for human topoisomerase II\u03b1","volume":"64","author":"Sandhaus","year":"2016","journal-title":"Inorg. Chem. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"8895","DOI":"10.1021\/ic401079w","article-title":"Copper(II) complexes with highly water-soluble L- and D-proline-thiosemicarbazone conjugates as potential inhibitors of Topoisomerase II\u03b1","volume":"52","author":"Bacher","year":"2013","journal-title":"Inorg. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jinorgbio.2015.08.008","article-title":"Quinoline-2-carboxaldehyde thiosemicarbazones and their Cu(II) and Ni(II) complexes as topoisomerase IIa inhibitors","volume":"152","author":"Bisceglie","year":"2015","journal-title":"J. Inorg. Biochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.taap.2004.02.004","article-title":"The cytotoxicity and mechanisms of 1,2-naphthoquinone thiosemicarbazone and its metal derivatives against MCF-7 human breast cancer cells","volume":"197","author":"Chen","year":"2004","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1021\/jm300938r","article-title":"In vitro and in vivo anticancer activity of copper bis(thiosemicarbazone) complexes","volume":"56","author":"Palanimuthu","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/mc.22610","article-title":"Molecular trail for the anticancer behavior of a novel copper carbohydrazone complex in BRCA1 mutated breast cancer","volume":"56","author":"Nair","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/chir.22081","article-title":"Enantiomeric specificity of biologically significant Cu(II) and Zn(II) chromone complexes towards DNA","volume":"24","author":"Arjmand","year":"2012","journal-title":"Chirality"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ejphar.2012.06.004","article-title":"Anti-cancer activity and mutagenic potential of novel copper(II) quinolinone Schiff base complexes in hepatocarcinoma cells","volume":"689","author":"Duff","year":"2012","journal-title":"Eur. J. Pharm."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"45229","DOI":"10.1038\/srep45229","article-title":"Heteroleptic copper(I) complexes of \u201cscorpionate\u201d bis-pyrazolyl carboxylate ligand with auxiliary phosphine as potential anticancer agents: An insight into cytotoxic mode","volume":"7","author":"Khan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_114","first-page":"5857","article-title":"Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage","volume":"44","author":"Ross","year":"1984","journal-title":"Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"20303","DOI":"10.1074\/jbc.M300198200","article-title":"Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes","volume":"278","author":"Furuta","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrc2523","article-title":"Gamma H2AX and cancer","volume":"8","author":"Bonner","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/embor.2009.97","article-title":"Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks","volume":"10","author":"Sordet","year":"2009","journal-title":"EMBO Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41571-018-0114-z","article-title":"State-of-the-art strategies for targeting the DNA damage response in cancer","volume":"16","author":"Tang","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/emboj.2008.15","article-title":"DNA-damage repair; the good, the bad and the ugly","volume":"27","author":"Hakem","year":"2008","journal-title":"EMBO J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/sj.embor.embor887","article-title":"Regulating mammalian checkpoints through Cdc25 inactivation","volume":"4","author":"Donzelli","year":"2003","journal-title":"EMBO Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1126\/science.281.5383.1674","article-title":"Enhanced phosphorylation of p53 by ATM in response to DNA damage","volume":"28","author":"Banin","year":"1998","journal-title":"Science"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1126\/science.281.5383.1677","article-title":"Activation of the ATM kinase by ionizing radiation and phosphorylation of p53","volume":"281","author":"Canman","year":"1998","journal-title":"Science"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1126\/science.287.5459.1824","article-title":"DNA damage-induced activation of p53 by the checkpoint kinase Chk2","volume":"287","author":"Hirao","year":"2000","journal-title":"Science"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1101\/gad.14.3.289","article-title":"The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites","volume":"14","author":"Shieh","year":"2000","journal-title":"Genes Dev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/366701a0","article-title":"p21 is a universal inhibitor of cyclin kinases","volume":"366","author":"Xiong","year":"1993","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1383-5742(98)00022-2","article-title":"Cyclin-dependent kinases at the G1-S transition of the mammalian cell cycle","volume":"436","author":"Braun","year":"1999","journal-title":"Mutat. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"6256","DOI":"10.1038\/sj.onc.1208759","article-title":"Diallyl trisulfide-induced G(2)-M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc 25 C","volume":"24","author":"Xiao","year":"2005","journal-title":"Oncogene"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1038\/bjc.2014.586","article-title":"Redox signalling to nuclear regulatory proteins by reactive oxygen species contributes to oestrogen-induced growth of breast cancer cells","volume":"112","author":"Okoh","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"6037","DOI":"10.1038\/sj.onc.1209629","article-title":"Oxidative stress induces a prolonged but reversible arrest in p53-null cancer cells, involving a Chk1-dependent G2 checkpoint","volume":"25","author":"Macip","year":"2006","journal-title":"Oncogene"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.bbrc.2011.05.032","article-title":"Asperlin induces G2\/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells","volume":"409","author":"He","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.cell.2017.01.002","article-title":"Endogenous DNA damage as a source of genomic instability in cancer","volume":"168","author":"Tubbs","year":"2017","journal-title":"Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1093\/nar\/gky1295","article-title":"A genome-wide RNAi screen identifies the SMC5\/6 complex as a non-redundant regulator of a Topo2a-dependent G2 arrest","volume":"47","author":"Deiss","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.4161\/cc.9.8.11470","article-title":"Revised genetic requirements for the decatenation G2 checkpoint: The role of ATM","volume":"9","author":"Bower","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4787","DOI":"10.1038\/onc.2010.232","article-title":"Topoisomerase IIalpha maintains genomic stability through decatenation G(2) checkpoint signaling","volume":"29","author":"Bower","year":"2010","journal-title":"Oncogene"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/j.1349-7006.2009.01408.x","article-title":"Analysis of inhibition of topoisomerase IIalpha and cancer cell proliferation by ingenolEZ","volume":"101","author":"Yoshida","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/nature12146","article-title":"BAF complexes facilitate decatenation of DNA by topoisomerase II\u03b1","volume":"497","author":"Dykhuizen","year":"2013","journal-title":"Nature"},{"key":"ref_137","first-page":"1504","article-title":"Topoisomerase II inhibitors and poisons, and the influence of cell cycle checkpoints","volume":"24","author":"Gabrielli","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41540-019-0104-5","article-title":"Identification of hyper-rewired genomic stress non-oncogene addiction genes across 15 cancer types","volume":"5","author":"Hjaltelin","year":"2019","journal-title":"NPJ Syst. Biol. Appl."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1002\/mc.23075","article-title":"CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death","volume":"58","author":"Holmes","year":"2019","journal-title":"Mol. Carcinog."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s12253-016-0163-5","article-title":"Systematic investigation of expression of G2\/M transition genes reveals CDC25 alteration in nonfunctioning pituitary adenomas","volume":"23","author":"Butz","year":"2017","journal-title":"Pathol. Oncol. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41418-018-0246-9","article-title":"Mutant p53 as a guardian of the cancer cell","volume":"26","author":"Mantovani","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/14737159.2019.1563484","article-title":"What is the potential of p53 isoforms as a predictive biomarker in the treatment of cancer?","volume":"19","author":"Hayman","year":"2019","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3389\/fonc.2018.00303","article-title":"Targeting cyclin-dependent kinases for treatment of gynecologic cancers","volume":"8","author":"Lin","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.phrs.2018.11.035","article-title":"Cyclin-dependent protein serine\/threonine kinase inhibitors as anticancer drugs","volume":"139","author":"Roskoski","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ejps.2016.03.025","article-title":"Cancer chemoresistance; biochemical and molecular aspects: A brief overview","volume":"89","author":"Kachalaki","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1476-4598-10-64","article-title":"New Topoisomerase I mutations are associated with resistance to camptothecin","volume":"10","author":"Gongora","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0169-5002(01)00425-1","article-title":"Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan","volume":"35","author":"Tsurutani","year":"2002","journal-title":"Lung Cancer"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bbamcr.2013.02.028","article-title":"The ubiquitin proteasome system\u2013implications for cell cycle control and the targeted treatment of cancer","volume":"1843","author":"Bassermann","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Lee, K.C., Swan, R.L., Sondka, Z., Padget, K., Cowell, I.G., and Austin, C.A. (2018). Effect of TDP2 on the Level of TOP2-DNA Complexes and SUMOylated TOP2-DNA Complexes. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072056"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"R53","DOI":"10.1186\/bcr2884","article-title":"Geminin overexpression prevents the completion of topoisomerase II\u03b1 chromosome decatenation, leading to aneuploidy in human mammary epithelial cells","volume":"13","author":"Gardner","year":"2011","journal-title":"Breast Cancer Res."},{"key":"ref_151","first-page":"382","article-title":"Casein kinase I delta phosphorylates topoisomerase II at serine-1106 and modulates DNA cleavage activity","volume":"37","author":"Rozav","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"13948","DOI":"10.1074\/jbc.275.18.13948","article-title":"Modulation of human DNA topoisomerase II function by interaction with 14\u20133-3\u201d","volume":"275","author":"Kurz","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s13046-016-0433-9","article-title":"Cell cycle checkpoint in cancer: A therapeutically targetable double-edged sword","volume":"35","author":"Visconti","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.1002\/j.1460-2075.1995.tb00182.x","article-title":"DNA damage in human B cells can induce apoptosis, proceeding from G1\/S when p53 is transactivation competent and G2\/M when it is transactivation defective","volume":"14","author":"Allday","year":"1995","journal-title":"EMBO J."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrm3115","article-title":"Mitotic catastrophe: A mechanism for avoiding genomic instability","volume":"12","author":"Vitale","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1101\/gad.290957.116","article-title":"ATR inhibition disrupts rewired homologous recombination and fork protection pathways in PARP inhibitor-resistant BRCA-deficient cancer cells","volume":"31","author":"Yazinski","year":"2017","journal-title":"Genes Dev."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12943-015-0321-5","article-title":"Apoptosis, autophagy, necroptosis, and cancer metastasis","volume":"14","author":"Su","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41580-018-0089-8","article-title":"Regulation of apoptosis in health and disease: The balancing act of BCL-2 family proteins","volume":"20","author":"Singh","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Pfeffer, C.M., and Singh, A.T.K. (2018). Apoptosis: A target for anticancer therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020448"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3537471","DOI":"10.1155\/2018\/3537471","article-title":"Regulation of tumor progression by programmed necrosis","volume":"2018","author":"Lee","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_161","first-page":"1835","article-title":"Intracellular ATP levels determine cell death fate by apoptosis or necrosis","volume":"57","author":"Eguchi","year":"1997","journal-title":"Cancer Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nri1415","article-title":"Inflammation and necrosis promote tumour growth","volume":"4","author":"Vakkila","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mam.2014.05.001","article-title":"MGB1 in health and disease","volume":"40","author":"Kang","year":"2014","journal-title":"Mol. Asp. Med."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Gomes, L.R., Menck, C.F.M., and Leandro, G.S. (2017). Autophagy roles in the modulation of DNA repair pathways. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112351"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.3892\/or.2015.4530","article-title":"Redox cycling of a copper complex with benzaldehyde nitrogen mustard-2-pyridine carboxylic acid hydrazone contributes to its enhanced antitumor activity, but no change in the mechanism of action occurs after chelation","volume":"3","author":"Yang","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/CAD.0000000000000572","article-title":"Autophagy and doxorubicin resistance in cancer","volume":"29","author":"Chen","year":"2018","journal-title":"Anticancer Drugs"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1042\/BCJ20160583","article-title":"Topoisomerases as anticancer targets","volume":"475","author":"Delgado","year":"2018","journal-title":"Biochem. J."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"104551","DOI":"10.1016\/j.phrs.2019.104551","article-title":"Topoisomerase inhibitors: Pharmacology and emerging nanoscale delivery systems","volume":"151","author":"Dehshahri","year":"2020","journal-title":"Pharm. Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"12234","DOI":"10.3748\/wjg.v21.i43.12234","article-title":"Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer","volume":"21","author":"Fujita","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.2147\/OTT.S167590","article-title":"Spotlight on liposomal irinotecan for metastatic pancreatic cancer: Patient selection and perspectives","volume":"12","author":"Woo","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1159\/000486622","article-title":"A Phase II Study of Irinotecan for Patients with Previously Treated Small-Cell Lung Cancer","volume":"94","author":"Kondo","year":"2018","journal-title":"Oncology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1186\/s12885-018-4715-9","article-title":"Irinotecan-platinum combination therapy for previously untreated extensive-stage small cell lung cancer patients: A meta-analysis","volume":"18","author":"Xu","year":"2018","journal-title":"BMC Cancer"},{"key":"ref_173","first-page":"CD005589","article-title":"Topotecan for ovarian cancer","volume":"2008","author":"Lihua","year":"2008","journal-title":"Cochrane Databse Syst. Rev."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1002\/cncr.32500","article-title":"Treatment of recurrent epithelial ovarian cancer","volume":"24","author":"Pignata","year":"2019","journal-title":"Cancer"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1097\/IGC.0000000000001000","article-title":"Systematic review and network meta-analysis of bevacizumab plus first-line topotecan-paclitaxel or cisplatin-paclitaxel versus non-bevacizumab-containing therapies in persistent, recurrent, or metastatic cervical cancer","volume":"27","author":"Rosen","year":"2017","journal-title":"Int. J. Gyn. Cancer"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1200\/JOP.18.00278","article-title":"Treatment options for relapsed small-cell lung cancer: What progress have we made?","volume":"14","author":"Qin","year":"2018","journal-title":"J. Oncol. Pract."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1200\/EDBK_100015","article-title":"Predicting and preventing anthracycline-related cardiotoxicity","volume":"38","author":"Armenian","year":"2018","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s11899-018-0436-z","article-title":"Update on the treatment of anaplastic large cell lymphoma","volume":"13","author":"Vu","year":"2018","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"42","DOI":"10.21037\/cco.2018.08.02","article-title":"Advances of systemic treatment for adult soft-tissue sarcoma","volume":"7","author":"Liu","year":"2018","journal-title":"Chin. Clin. Oncol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1002\/cncr.32795","article-title":"European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first-line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group","volume":"126","author":"Touati","year":"2020","journal-title":"Cancer"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.2174\/092986709788803312","article-title":"Doxorubicin: The good, the bad and the ugly effect","volume":"16","author":"Carvalho","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1002\/ejhf.1168","article-title":"Long-term effect of epirubicin on incidence of heart failure in women with breast cancer: Insight from a randomized clinical trial","volume":"20","author":"Banke","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1007\/s00345-018-2592-0","article-title":"Emerging therapies in the management of high-risk non-muscle invasive bladder cancer (HRNMIBC)","volume":"37","author":"Werntz","year":"2019","journal-title":"World J. Urol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e480","DOI":"10.1016\/S2352-3026(19)30114-0","article-title":"Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: A single-arm, phase 2 study","volume":"6","author":"Ravandi","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/med.21364","article-title":"Mitoxantrone, More than Just another topoisomerase II poison","volume":"36","author":"Evison","year":"2016","journal-title":"Med. Res. Rev."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1007\/s00277-019-03749-0","article-title":"Pixantrone beyond monotherapy: A review","volume":"98","author":"Toldbod","year":"2019","journal-title":"Ann. Hematol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1080\/17474086.2018.1476848","article-title":"Pixantrone: Novel mode of action and clinical readouts","volume":"11","author":"Minotti","year":"2018","journal-title":"Expert Rev. Hematol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1080\/14656566.2019.1583745","article-title":"Current pharmacotherapy for testicular germ cell cancer","volume":"20","author":"Alsdorf","year":"2019","journal-title":"Expert Opin. Pharm."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/978-3-319-40389-2_14","article-title":"Small Cell Lung Cancer","volume":"170","author":"Bernhardt","year":"2016","journal-title":"Cancer Treat. Res."},{"key":"ref_190","first-page":"CD007464","article-title":"Chemotherapy for brain metastases from small cell lung cancer","volume":"6","author":"Reveiz","year":"2012","journal-title":"Cochrane Databse Syst. Rev."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1477-7819-4-41","article-title":"Topoisomerase II trapping agent teniposide induces apoptosis and G2\/M or S phase arrest of oral squamous cell carcinoma","volume":"4","author":"Li","year":"2006","journal-title":"World J. Surg. Oncol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/MPH.0b013e318279afdd","article-title":"Chemotherapy for initial induction failures in childhood acute lymphoblastic leukemia: A Children\u2019s Oncology Group Study (POG 8764)","volume":"35","author":"Joyce","year":"2013","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"37286","DOI":"10.18632\/oncotarget.26466","article-title":"Novel clinical indenoisoquinoline topoisomerase I inhibitors: A twist around the camptothecins","volume":"9","author":"Pommier","year":"2018","journal-title":"Oncotarget"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1021\/cr200325f","article-title":"Contemporary challenges in the design of topoisomerase II inhibitors for cancer chemotherapy","volume":"112","author":"Bailly","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13321-019-0390-3","article-title":"Identifying new topoisomerase II poison scaffolds by combining publicly available toxicity data and 2D\/3D-based virtual screening","volume":"11","author":"Lovrics","year":"2019","journal-title":"J. Cheminform."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1021\/acs.jmedchem.7b01388","article-title":"Pharmacophore hybridization to discover novel topoisomerase II poisons with promising antiproliferative activity","volume":"61","author":"Ortega","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1021\/acs.jmedchem.5b00303","article-title":"Discovery of potent indenoisoquinoline topoisomerase I poisons lacking the 3-nitro toxicophore","volume":"58","author":"Beck","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nrc2607","article-title":"Targeting DNA topoisomerase II in cancer chemotherapy","volume":"9","author":"Nitiss","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13550-020-00621-5","article-title":"Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: A review of current evidence and discussion of the retention mechanisms","volume":"10","author":"Liu","year":"2020","journal-title":"Ejnmmi Res."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ajh.24246","article-title":"Acute myeloid leukemia-Major progress over four decades and glimpses into the future","volume":"91","author":"Kantarjian","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/S1470-2045(15)00165-5","article-title":"Vosaroxin in acute myeloid leukaemia","volume":"16","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1021\/acs.jmedchem.9b00726","article-title":"Dual inhibitors of human DNA topoisomerase II and other cancer-related targets","volume":"63","author":"Skok","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Kim, S.O., Sakchaisri, K., Thimmegowda, N.R., Soung, N.K., Jang, J.H., Kim, Y.S., Lee, K.S., Kwon, Y.T., Asami, Y., and Ahn, J.S. (2013). STK295900, a dual inhibitor of topoisomerase 1 and 2, induces G(2) arrest in the absence of DNA damage. PLoS ONE, 8.","DOI":"10.1371\/annotation\/c5f432f6-1e92-42c0-8727-7ae972215d6f"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"8960","DOI":"10.18632\/oncotarget.3264","article-title":"Dual targeting of microtubule and topoisomerase II by \u03b1-carboline derivative YCH337 for tumor proliferation and growth inhibition","volume":"6","author":"Yi","year":"2015","journal-title":"Oncotarget"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"85","DOI":"10.15430\/JCP.2015.20.2.85","article-title":"Dual inhibitors against topoisomerases and histone deacetylases","volume":"20","author":"Seo","year":"2015","journal-title":"J. Cancer Prev."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Ferreira, R., Schneekloth, J.S., Panov, K.I., Hannan, K.M., and Hannan, R.D. (2020). Targeting the RNA polymerase I transcription for cancer therapy comes of age. Cells, 9.","DOI":"10.3390\/cells9020266"},{"key":"ref_207","first-page":"9706792","article-title":"The specific inhibition of SOD1 selectively promotes apoptosis of cancer cells via regulation of the ROS signaling network","volume":"2019","author":"Li","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/35030140","article-title":"Superoxide dismutase as a target for the selective killing of cancer cells","volume":"407","author":"Huang","year":"2000","journal-title":"Nature"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Ceci, C., Atzori, M.G., Lacal, P.M., and Graziani, G. (2020). Role of VEGFs\/VEGFR-1 signaling and its inhibition in modulating tumor invasion: Experimental evidence in different metastatic cancer models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041388"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"104609","DOI":"10.1016\/j.phrs.2019.104609","article-title":"Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update","volume":"152","author":"Roskoski","year":"2020","journal-title":"Pharm. Res."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"11534","DOI":"10.1073\/pnas.93.21.11534","article-title":"A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases","volume":"93","author":"Yang","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature08444","article-title":"A human 5\u2019-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage","volume":"461","author":"Zuma","year":"2009","journal-title":"Nature"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1002\/med.21587","article-title":"Dual DNA topoisomerase 1 and tyrosyl-DNA phosphodiesterase 1 inhibition for improved anticancer activity","volume":"39","author":"Zakharenko","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2018.02.039","article-title":"Suppressing autophagy enhances disulfiram\/copper-induced apoptosis in non-small cell lung cancer","volume":"827","author":"Wu","year":"2018","journal-title":"Eur. J. Pharm."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Marinello, J., Delcuratolo, M., and Capranico, G. (2018). Anthracyclines as topoisomerase II poisons: From early studies to new perspectives. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113480"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/bjc.2017.376","article-title":"Combining DNA damaging therapeutics with immunotherapy: More haste, less speed","volume":"118","author":"Brown","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/annonc\/mdy551","article-title":"Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors","volume":"30","author":"Heinhuis","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.dnarep.2017.06.005","article-title":"The Top1 paradox: Friend and foe of the eukaryotic genome","volume":"56","author":"Kim","year":"2017","journal-title":"DNA Repair"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18632\/oncotarget.7277","article-title":"Association and prognostic significance of BRCA1\/2-mutation status with neoantigen load, number of tumorinfiltrating lymphocytes and expression of PD-1\/PD-L1 in high grade serous ovarian cancer","volume":"7","author":"Strickland","year":"2016","journal-title":"Oncotarget"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13045-019-0721-x","article-title":"Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy","volume":"12","author":"Li","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41467-020-14652-y","article-title":"Topoisomerase 1 cleavage complex enables pattern recognition and inflammation during senescence","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1172\/JCI127471","article-title":"cGAS\/STING axis mediates a topoisomerase II inhibitor-induced tumor immunogenicity","volume":"130","author":"Wang","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Wilkinson, R.D.A., McCabe, N., Parkes, E.E., Barros, E.M., Johnston, D.I., Ali, R.M.M., Lappin, K., Greenberg, R.A., Harkin, D.P., and McIntosh, S.A. (2019). Topoisomerase II inhibitors induce cGAS-STING dependent inflammation resulting in cytokine induction and immune checkpoint activation. bioRxiv.","DOI":"10.1101\/764662"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"101084","DOI":"10.1016\/j.redox.2018.101084","article-title":"ROS and the DNA damage response in cancer","volume":"25","author":"Srinivas","year":"2019","journal-title":"Redox Biol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"eaav1898","DOI":"10.1126\/science.aav1898","article-title":"The chromatin accessibility landscape of primary human cancers","volume":"362","author":"Corces","year":"2018","journal-title":"Science"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1038\/s41467-018-04208-6","article-title":"The effects of mutational processes and selection on driver mutations across cancer types","volume":"9","author":"Temko","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1093\/carcin\/bgq064","article-title":"Homologous recombination in cancer development, treatment and development of drug resistance","volume":"31","author":"Helleday","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1010428317695931","DOI":"10.1177\/1010428317695931","article-title":"gamma-H2AX: Can it be established as a classical cancer prognostic factor?","volume":"39","author":"Palla","year":"2017","journal-title":"Tumour Biol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.pharmthera.2019.05.009","article-title":"Schlafen 11 (SLFN11), a restriction factor for replicative stress induced by DNA-targeting anti-cancer therapies","volume":"201","author":"Murai","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1093\/nar\/gky072","article-title":"Coupling the core of the anticancer drug etoposide to an oligonucleotide induces topoisomerase II-mediated cleavage at specific DNA sequences","volume":"46","author":"Fenner","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1080\/10717544.2017.1396384","article-title":"Synergistic dual-modified liposome improves targeting and therapeutic efficacy of bone metastasis from breast cancer","volume":"24","author":"Ke","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_233","first-page":"1311","article-title":"Chemotherapeutic effect of CD147antibody-labeled micelles encapsulating doxorubicin conjugate targeting cd147-expressing carcinoma cells","volume":"38","author":"Asakura","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"8257","DOI":"10.2147\/IJN.S143776","article-title":"A nanoliposome-based photoactivable drug delivery system for enhanced cancer therapy and overcoming treatment resistance","volume":"12","author":"Shi","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Goffart, S., Hangas, A., and Pohjoism\u00e4ki, J.L.O. (2019). Twist and Turn-Topoisomerase Functions in Mitochondrial DNA Maintenance. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20082041"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41467-018-07922-3","article-title":"The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis","volume":"10","author":"Baechler","year":"2019","journal-title":"Nat. Commun."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/10\/2863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:16:37Z","timestamp":1760177797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/10\/2863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,5]]},"references-count":236,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["cancers12102863"],"URL":"https:\/\/doi.org\/10.3390\/cancers12102863","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,5]]}}}