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and Innova-tion of Spain","award":["Grant No. 826121 (iPC)"],"award-info":[{"award-number":["Grant No. 826121 (iPC)"]}]},{"name":"Ram\u00f3n y Cajal grant of the Ministry of Science and Innova-tion of Spain","award":["668596 (ChiLTERN)"],"award-info":[{"award-number":["668596 (ChiLTERN)"]}]},{"name":"Ram\u00f3n y Cajal grant of the Ministry of Science and Innova-tion of Spain","award":["Grant No. 201908080285"],"award-info":[{"award-number":["Grant No. 201908080285"]}]},{"name":"Ram\u00f3n y Cajal grant of the Ministry of Science and Innova-tion of Spain","award":["2019_FI_B01024"],"award-info":[{"award-number":["2019_FI_B01024"]}]},{"name":"Ram\u00f3n y Cajal grant of the Ministry of Science and Innova-tion of Spain","award":["2022_FI_B00528"],"award-info":[{"award-number":["2022_FI_B00528"]}]},{"name":"Ram\u00f3n y Cajal grant of the Ministry of Science and Innova-tion of Spain","award":["(RYC-2010-07249)"],"award-info":[{"award-number":["(RYC-2010-07249)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Resistance to conventional chemotherapy remains a huge challenge in the clinical management of hepatoblastoma, the most common liver tumor in childhood. By integrating the gene expression data of hepatoblastoma patients into the perturbation prediction tool Connectivity Map, we identified the clinical widely used anthelmintic mebendazole as a drug to circumvent chemoresistance in permanent and patient-derived xenograft cell lines that are resistant to cisplatin, the therapeutic backbone of hepatoblastoma treatment. Viability assays clearly indicated a potent reduction of tumor cell growth upon mebendazole treatment in a dose-dependent manner. The combination of mebendazole and cisplatin revealed a strong synergistic effect, which was comparable to the one seen with cisplatin and doxorubicin, the current treatment for high-risk hepatoblastoma patients. Moreover, mebendazole treatment resulted in reduced colony and tumor spheroid formation capabilities, cell cycle arrest, and induction of apoptosis of hepatoblastoma cells. Mechanistically, mebendazole causes blockage of microtubule formation and transcriptional downregulation of genes encoding the unwindosome, which are highly expressed in chemoresistant tumors. Most importantly, mebendazole significantly reduced tumor growth in a subcutaneous xenograft transplantation mouse model without side effects. In conclusion, our results strongly support the clinical use of mebendazole in the treatment of chemoresistant hepatoblastoma and highlight the potential theranostic value of unwindosome-associated genes.<\/jats:p>","DOI":"10.3390\/cancers14174196","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T21:25:18Z","timestamp":1661894718000},"page":"4196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting the Unwindosome by Mebendazole Is a Vulnerability of Chemoresistant Hepatoblastoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Qian","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salih","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Del R\u00edo-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Childhood Liver Oncology Group, Health Sciences Research Institute Germans Trias i Pujol IGTP, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Carrillo-Reixach","sequence":"additional","affiliation":[{"name":"Childhood Liver Oncology Group, Health Sciences Research Institute Germans Trias i Pujol IGTP, 08916 Badalona, Spain"},{"name":"Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4690-4027","authenticated-orcid":false,"given":"Carolina","family":"Armengol","sequence":"additional","affiliation":[{"name":"Childhood Liver Oncology Group, Health Sciences Research Institute Germans Trias i Pujol IGTP, 08916 Badalona, Spain"},{"name":"Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vokuhl","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"H\u00e4berle","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"von Schweinitz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cairo","sequence":"additional","affiliation":[{"name":"XenTech, 91000 Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-2803","authenticated-orcid":false,"given":"Roland","family":"Kappler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/MOP.0000000000000046","article-title":"Hepatoblastoma state of the art: Pathology, genetics, risk stratification, and chemotherapy","volume":"26","author":"Czauderna","year":"2014","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/pbc.24213","article-title":"Genetics and epigenetics of hepatoblastoma","volume":"59","author":"Tomlinson","year":"2012","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/j.jhep.2014.08.009","article-title":"The genomic landscape of hepatoblastoma and their progenies with HCC-like features","volume":"61","author":"Trippel","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1158\/2159-8290.CD-20-1809","article-title":"Integrated Genomic Analysis Identifies Driver Genes and Cisplatin-Resistant Progenitor Phenotype in Pediatric Liver Cancer","volume":"11","author":"Hirsch","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5423","DOI":"10.1038\/s41467-021-25430-9","article-title":"Genetic and epigenetic basis of hepatoblastoma diversity","volume":"12","author":"Nagae","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/hep.28888","article-title":"Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups","volume":"65","author":"Sumazin","year":"2017","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1056\/NEJMoa0810613","article-title":"Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma","volume":"361","author":"Perilongo","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1200\/JCO.2009.22.4857","article-title":"Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: Final results of the SIOPEL-3HR study","volume":"28","author":"Zsiros","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nrc2044","article-title":"The Connectivity Map: A new tool for biomedical research","volume":"7","author":"Lamb","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/j.drudis.2012.07.017","article-title":"Applications of Connectivity Map in drug discovery and development","volume":"17","author":"Qu","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Claerhout, S., Lim, J.Y., Choi, W., Park, Y.Y., Kim, K., Kim, S.B., Lee, J.S., Mills, G.B., and Cho, J.Y. (2011). Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024662"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ccr.2006.09.005","article-title":"Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators","volume":"10","author":"Hieronymus","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ccr.2006.09.006","article-title":"Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance","volume":"10","author":"Wei","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccr.2008.11.002","article-title":"Hepatic stem-like phenotype and interplay of Wnt\/beta-catenin and Myc signaling in aggressive childhood liver cancer","volume":"14","author":"Cairo","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jhep.2020.03.025","article-title":"Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications","volume":"73","author":"Torrens","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/hep.29672","article-title":"New insights into diagnosis and therapeutic options for proliferative hepatoblastoma","volume":"68","author":"Hooks","year":"2018","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejca.2020.09.026","article-title":"A combined clinical and biological risk classification improves prediction of outcome in hepatoblastoma patients","volume":"141","author":"Cairo","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wagner, A.E., Schwarzmayr, T., Haberle, B., Vokuhl, C., Schmid, I., von Schweinitz, D., and Kappler, R. (2020). SP8 Promotes an Aggressive Phenotype in Hepatoblastoma via FGF8 Activation. Cancers, 12.","DOI":"10.3390\/cancers12082294"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1055\/a-1014-3250","article-title":"High Dose Chemotherapy with Autologous Stem Cell Transplantation in Hepatoblastoma does not Improve Outcome. Results of the GPOH Study HB99","volume":"231","author":"Haberle","year":"2019","journal-title":"Klin. Padiatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The Connectivity Map: Using gene-expression signatures to connect small molecules, genes, and disease","volume":"313","author":"Lamb","year":"2006","journal-title":"Science"},{"key":"ref_22","first-page":"809","article-title":"Characterization of the continuous cell line HepT1 derived from a human hepatoblastoma","volume":"74","author":"Pietsch","year":"1996","journal-title":"Lab. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/hep.28621","article-title":"Patient-derived mouse xenografts from pediatric liver cancer predict tumor recurrence and advise clinical management","volume":"64","author":"Nicolle","year":"2016","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"W488","DOI":"10.1093\/nar\/gkaa216","article-title":"SynergyFinder 2.0: Visual analytics of multi-drug combination synergies","volume":"48","author":"Ianevski","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_25","first-page":"51639","article-title":"High-throughput image analysis of tumor spheroids: A user-friendly software application to measure the size of spheroids automatically and accurately","volume":"89","author":"Chen","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1016\/j.ejca.2011.12.032","article-title":"Rapamycin blocks hepatoblastoma growth in vitro and in vivo implicating new treatment options in high-risk patients","volume":"48","author":"Wagner","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1158\/1078-0432.CCR-08-2878","article-title":"Activation of phosphatidylinositol-3\u2032-kinase\/AKT signaling is essential in hepatoblastoma survival","volume":"15","author":"Hartmann","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/282615a0","article-title":"Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line","volume":"282","author":"Aden","year":"1979","journal-title":"Nature"},{"key":"ref_33","first-page":"151","article-title":"Phenotypical stability of a human hepatoma cell line, HuH-7, in long-term culture with chemically defined medium","volume":"75","author":"Nakabayashi","year":"1984","journal-title":"Gan"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.3389\/fonc.2020.01138","article-title":"Chloroquine Triggers Cell Death and Inhibits PARPs in Cell Models of Aggressive Hepatoblastoma","volume":"10","author":"Eloranta","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S1470-2045(13)70272-9","article-title":"Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): A prospective, single-arm, feasibility study","volume":"14","author":"Zsiros","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0006-291X(80)90349-6","article-title":"Inhibition of tubulin polymerization by mebendazole","volume":"92","author":"Laclette","year":"1980","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Draber, P., and Draberova, E. (2021). Dysregulation of Microtubule Nucleating Proteins in Cancer Cells. Cancers, 13.","DOI":"10.3390\/cancers13225638"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1083\/jcb.201806057","article-title":"CDK1-mediated phosphorylation at H2B serine 6 is required for mitotic chromosome segregation","volume":"218","author":"Seibert","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrm2163","article-title":"The spindle-assembly checkpoint in space and time","volume":"8","author":"Musacchio","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fmolb.2018.00026","article-title":"The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy","volume":"5","author":"Seo","year":"2018","journal-title":"Front. Mol. Biosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00247-006-0361-5","article-title":"2005 PRETEXT: A revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group","volume":"37","author":"Roebuck","year":"2007","journal-title":"Pediatr. Radiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/S1470-2045(16)30598-8","article-title":"Risk-stratified staging in paediatric hepatoblastoma: A unified analysis from the Children\u2019s Hepatic tumors International Collaboration","volume":"18","author":"Meyers","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3910","DOI":"10.1039\/C5AN00524H","article-title":"Chemical analysis of multicellular tumour spheroids","volume":"140","author":"Jamieson","year":"2015","journal-title":"Analyst"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/534314a","article-title":"Can you teach old drugs new tricks?","volume":"534","author":"Nosengo","year":"2016","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/S0140-6736(06)68653-4","article-title":"Soil-transmitted helminth infections: Ascariasis, trichuriasis, and hookworm","volume":"367","author":"Bethony","year":"2006","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0001-706X(03)00042-1","article-title":"Use of benzimidazoles in children younger than 24 months for the treatment of soil-transmitted helminthiasis","volume":"86","author":"Montresor","year":"2003","journal-title":"Acta Trop."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/jac\/46.3.451","article-title":"Benzimidazoles in the treatment of alveolar echinococcosis: A comparative study and review of the literature","volume":"46","author":"Reuter","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1093\/neuonc\/nor077","article-title":"Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme","volume":"13","author":"Bai","year":"2011","journal-title":"Neuro Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/CAD.0b013e32835a43f1","article-title":"XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts","volume":"24","author":"Doudican","year":"2013","journal-title":"Anticancer Drugs"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s00280-007-0538-0","article-title":"Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice","volume":"61","author":"Martarelli","year":"2008","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_51","first-page":"2963","article-title":"Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo","volume":"8","author":"Mukhopadhyay","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"68571","DOI":"10.18632\/oncotarget.11851","article-title":"Mebendazole and a non-steroidal anti-inflammatory combine to reduce tumor initiation in a colon cancer preclinical model","volume":"7","author":"Williamson","year":"2016","journal-title":"Oncotarget"},{"key":"ref_53","first-page":"vdaa154","article-title":"Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: Results of a phase 1 clinical trial","volume":"3","author":"Gallia","year":"2021","journal-title":"Neurooncol. Adv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8981","DOI":"10.1038\/s41598-021-88433-y","article-title":"A phase 2a clinical study on the safety and efficacy of individualized dosed mebendazole in patients with advanced gastrointestinal cancer","volume":"11","author":"Mansoori","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"120536","DOI":"10.1016\/j.lfs.2022.120536","article-title":"Mebendazole; from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer","volume":"299","author":"Hegazy","year":"2022","journal-title":"Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Guerini, A.E., Triggiani, L., Maddalo, M., Bonu, M.L., Frassine, F., Baiguini, A., Alghisi, A., Tomasini, D., Borghetti, P., and Pasinetti, N. (2019). Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature. Cancers, 11.","DOI":"10.3390\/cancers11091284"},{"key":"ref_57","first-page":"1707","article-title":"E2F1-mediated GINS2 transcriptional activation promotes tumor progression through PI3K\/AKT\/mTOR pathway in hepatocellular carcinoma","volume":"12","author":"Zhang","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1010428317705342","DOI":"10.1177\/1010428317705342","article-title":"Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle","volume":"39","author":"Sun","year":"2017","journal-title":"Tumour. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1158\/1541-7786.MCR-14-0464","article-title":"Suppression of Reserve MCM Complexes Chemosensitizes to Gemcitabine and 5-Fluorouracil","volume":"13","author":"Bryant","year":"2015","journal-title":"Mol. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrc2167","article-title":"The resurgence of platinum-based cancer chemotherapy","volume":"7","author":"Kelland","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17407","DOI":"10.18632\/aging.203232","article-title":"Antiparasitic mebendazole (MBZ) effectively overcomes cisplatin resistance in human ovarian cancer cells by inhibiting multiple cancer-associated signaling pathways","volume":"13","author":"Huang","year":"2021","journal-title":"Aging"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/17\/4196\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:19:58Z","timestamp":1760141998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/17\/4196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,30]]},"references-count":61,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cancers14174196"],"URL":"https:\/\/doi.org\/10.3390\/cancers14174196","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,30]]}}}