{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:13:20Z","timestamp":1768871600036,"version":"3.49.0"},"reference-count":219,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","doi-asserted-by":"publisher","award":["UID\/QUI\/50006\/2020"],"award-info":[{"award-number":["UID\/QUI\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Neuroblastoma (NB) is an embryonic cancer that develops from neural crest stem cells, being one of the most common malignancies in children. The clinical manifestation of this disease is highly variable, ranging from spontaneous regression to increased aggressiveness, which makes it a major therapeutic challenge in pediatric oncology. The p53 family proteins p53 and TAp73 play a key role in protecting cells against genomic instability and malignant transformation. However, in NB, their activities are commonly inhibited by interacting proteins such as murine double minute (MDM)2 and MDMX, mutant p53, \u0394Np73, Itch, and Aurora kinase A. The interplay between the p53\/TAp73 pathway and N-MYC, a known biomarker of poor prognosis and drug resistance in NB, also proves to be decisive in the pathogenesis of this tumor. More recently, a strong crosstalk between microRNAs (miRNAs) and p53\/TAp73 has been established, which has been the focused of great attention because of its potential for developing new therapeutic strategies. Collectively, this review provides an updated overview about the critical role of the p53\/TAp73 pathway in the pathogenesis of NB, highlighting encouraging clues for the advance of alternative NB targeted therapies.<\/jats:p>","DOI":"10.3390\/cancers14246212","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T03:55:39Z","timestamp":1671162939000},"page":"6212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2325-5439","authenticated-orcid":false,"given":"Joana","family":"Almeida","sequence":"first","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"In\u00eas","family":"Mota","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9292-8177","authenticated-orcid":false,"given":"Jan","family":"Skoda","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology, Faculty of Science, Masaryk University, 62500 Brno, Czech Republic"},{"name":"International Clinical Research Center, St. Anne\u2019s University Hospital, 65691 Brno, Czech Republic"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-4672","authenticated-orcid":false,"given":"Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-1779","authenticated-orcid":false,"given":"Honorina","family":"Cidade","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/nm.4409","article-title":"Cancer stem cells revisited","volume":"23","author":"Batlle","year":"2017","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1021820","DOI":"10.3389\/fcell.2022.1021820","article-title":"Targeting bromodomain and extra-terminal proteins to inhibit neuroblastoma tumorigenesis through regulating MYCN","volume":"10","author":"Shi","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jpedsurg.2018.09.004","article-title":"Update on neuroblastoma","volume":"54","author":"Newman","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/s41588-021-00818-x","article-title":"Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin","volume":"53","author":"Kameneva","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/s41588-021-00806-1","article-title":"Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma","volume":"53","author":"Jansky","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e108780","DOI":"10.15252\/embj.2021108780","article-title":"Schwann cell precursors represent a neural crest-like state with biased multipotency","volume":"41","author":"Kastriti","year":"2022","journal-title":"EMBO J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"16078","DOI":"10.1038\/nrdp.2016.78","article-title":"Neuroblastoma","volume":"2","author":"Matthay","year":"2016","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s11912-022-01270-8","article-title":"Neuroblastoma Heterogeneity, Plasticity, and Emerging Therapies","volume":"24","author":"Lundberg","year":"2022","journal-title":"Curr. Oncol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2010","DOI":"10.1038\/cddis.2015.354","article-title":"Neuroblastoma: Oncogenic mechanisms and therapeutic exploitation of necroptosis","volume":"6","author":"Nicolai","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/jjco\/hyx176","article-title":"Neuroblastoma","volume":"48","author":"Nakagawara","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.hoc.2009.11.011","article-title":"Neuroblastoma: Biology, Prognosis, and Treatment","volume":"24","author":"Park","year":"2010","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ccell.2014.09.019","article-title":"ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma","volume":"26","author":"Bresler","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/nature07261","article-title":"Identification of ALK as a major familial neuroblastoma predisposition gene","volume":"455","author":"Laudenslager","year":"2008","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nature07398","article-title":"Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma","volume":"455","author":"Lequin","year":"2008","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pacak, K., and Ta\u00efeb, D. (2017). Molecular Genetics of Neuroblastoma. Diagnostic and Therapeutic Nuclear Medicine for Neuroendocrine Tumors, Humana Press.","DOI":"10.1007\/978-3-319-46038-3"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00018-020-03609-5","article-title":"Neuronal lineages derived from the nerve-associated Schwann cell precursors","volume":"78","author":"Kameneva","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1086\/424530","article-title":"Germline PHOX2B Mutation in Hereditary Neuroblastoma","volume":"75","author":"Mosse","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1086\/383253","article-title":"Germline Mutations of the Paired-Like Homeobox 2B (PHOX2B) Gene in Neuroblastoma","volume":"74","author":"Trochet","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/ng.3438","article-title":"TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors","volume":"47","author":"Valentijn","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1158\/1078-0432.CCR-08-1815","article-title":"Trk receptor expression and inhibition in neuroblastomas","volume":"15","author":"Brodeur","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1073\/pnas.0910684107","article-title":"High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset","volume":"107","author":"Kryh","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13806","DOI":"10.1038\/s41598-019-50327-5","article-title":"Clinical Features of Neuroblastoma With 11q Deletion: An Increase in Relapse Probabilities In Localized And 4S Stages","volume":"9","author":"Gargallo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/1096-911X(20001201)35:6<512::AID-MPO2>3.0.CO;2-D","article-title":"Identification of a 1-megabase consensus region of deletion at 1p36.3 in Primary neuroblastomas","volume":"35","author":"Hogarty","year":"2000","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/sj.onc.1202390","article-title":"P73 At Chromosome 1P36.3 Is Lost in Advanced Stage Neuroblastoma But Its Mutation Is Infrequent","volume":"18","author":"Ichimiya","year":"1999","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/cdd.2010.35","article-title":"P53-family proteins and their regulators: Hubs and spokes in tumor suppression","volume":"17","author":"Collavin","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105245","DOI":"10.1016\/j.phrs.2020.105245","article-title":"p73: From the p53 shadow to a major pharmacological target in anticancer therapy","volume":"162","author":"Ramos","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, C., Teo, C.R., and Sabapathy, K. (2020). P53-related transcription targets of TAp73 in cancer cells\u2014Bona fide or distorted reality?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041346"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/19539","article-title":"P63 Is Essential for Regenerative Proliferation in Limb, Craniofacial and Epithelial Development","volume":"398","author":"Yang","year":"1999","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/35003607","article-title":"p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours","volume":"404","author":"Yang","year":"2000","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"687359","DOI":"10.1155\/2012\/687359","article-title":"P53 family: Role of protein isoforms in human cancer","volume":"2012","author":"Wei","year":"2012","journal-title":"J. Nucleic Acids"},{"key":"ref_31","first-page":"a004887","article-title":"P63 and P73, the Ancestors of P53","volume":"2","author":"Bernassola","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nrc2072","article-title":"The p53 family in differentiation and tumorigenesis","volume":"7","author":"Stiewe","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrm2147","article-title":"P53 in Health and Disease","volume":"8","author":"Vousden","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.semcancer.2010.02.005","article-title":"P53 family members in cancer diagnosis and treatment","volume":"20","author":"Perrier","year":"2010","journal-title":"Semin. Cancer Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1046\/j.1440-1827.2000.01090.x","article-title":"p73: Structure and function","volume":"50","author":"Ichimiya","year":"2000","journal-title":"Pathol. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15226","DOI":"10.1074\/jbc.275.20.15226","article-title":"Induction of neuronal differentiation by p73 in a neuroblastoma cell line","volume":"275","author":"Barcaroli","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/jcb.22094","article-title":"New therapeutic targets for the treatment of high-risk neuroblastoma","volume":"107","author":"Wagner","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_38","first-page":"5269","article-title":"Absence of p53 Gene Mutations in Primary Neuroblastomas","volume":"53","author":"Vogan","year":"1993","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/sj.neo.7900255","article-title":"N-myc modulates expression of p73 in neuroblastoma","volume":"4","author":"Zhu","year":"2002","journal-title":"Neoplasia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/sj.cdd.4400631","article-title":"p53 family genes: Structural comparison, expression and mutation","volume":"6","author":"Ikawa","year":"1999","journal-title":"Cell Death Differ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.31768\/2312-8852.2015.37(2):111-115","article-title":"Prognostic significance of MDM2 gene expression in childhood neuroblastoma","volume":"37","author":"Inomistova","year":"2015","journal-title":"Exp. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-94-017-9211-0_15","article-title":"Mdm2 and MdmX involvement in human cancer","volume":"Volume 85","author":"Berberich","year":"2014","journal-title":"Sub-Cellular Biochemistry"},{"key":"ref_43","first-page":"1081","article-title":"Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma","volume":"10","author":"Corvi","year":"1995","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2174\/1568009053332636","article-title":"MDM2 and human malignancies: Expression, clinical pathology, prognostic markers, and implications for chemotherapy","volume":"5","author":"Rayburn","year":"2005","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.canlet.2020.09.023","article-title":"Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope","volume":"496","author":"Zafar","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrc3430","article-title":"MDM2, MDMX and p53 in oncogenesis and cancer therapy","volume":"13","author":"Wade","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1146\/annurev-pathol-012414-040349","article-title":"The Roles of MDM2 and MDMX in Cancer","volume":"11","author":"Lokshin","year":"2016","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1038\/sj.onc.1202781","article-title":"Mdm2 binds p73\u03b1 without targeting degradation","volume":"18","author":"Bates","year":"1999","journal-title":"Oncogene"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1038\/sj.onc.1202512","article-title":"Inactivation of the p53-homologue p73 by the mdm2-oncoprotein","volume":"18","author":"Dobbelstein","year":"1999","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"21479","DOI":"10.18632\/oncotarget.4086","article-title":"MDM2 mediates p73 ubiquitination: A new molecular mechanism for suppression of p73 function","volume":"6","author":"Wu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8533","DOI":"10.1128\/MCB.21.24.8533-8546.2001","article-title":"Identification of p53 Sequence Elements That Are Required for MDM2-Mediated Nuclear Export","volume":"21","author":"Gu","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1016\/j.ejca.2010.05.026","article-title":"HDM2 impairs Noxa transcription and affects apoptotic cell death in a p53\/p73-dependent manner in neuroblastoma","volume":"46","author":"Shi","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1158\/1535-7163.MCT-06-0305","article-title":"MDM2 inhibition sensitizes neuroblastoma to chemotherapy-induced apoptotic cell death","volume":"5","author":"Barbieri","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9646","DOI":"10.1158\/0008-5472.CAN-06-0792","article-title":"Small-molecule MDM2 antagonists as a new therapy concept for neuroblastoma","volume":"66","author":"Speleman","year":"2006","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/onc.2011.270","article-title":"MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63","volume":"31","author":"Gamble","year":"2012","journal-title":"Oncogene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"818744","DOI":"10.3389\/fcell.2022.818744","article-title":"It\u2019s Getting Complicated\u2014A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy","volume":"10","author":"Kung","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/cdd.2009.138","article-title":"Escape from p53-mediated tumor surveillance in neuroblastoma: Switching off the p14ARF-MDM2-p53 axis","volume":"16","author":"Vandesompele","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1158\/1078-0432.CCR-09-1865","article-title":"High frequency of p53\/MDM2\/p14ARF pathway abnormalities in relapsed neuroblastoma","volume":"16","author":"Wood","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gomes, A.S., Ramos, H., Inga, A., Sousa, E., and Saraiva, L. (2021). Structural and drug targeting insights on mutant p53. Cancers, 13.","DOI":"10.3390\/cancers13133344"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ncb2641","article-title":"P53 mutations in cancer","volume":"15","author":"Muller","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1101\/gad.6.10.1886","article-title":"Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53","volume":"6","author":"Bargonetti","year":"1992","journal-title":"Genes Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1126\/science.256.5058.827","article-title":"Oncogenic forms of p53 inhibit p53-regulated gene expression","volume":"256","author":"Kern","year":"1992","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1128\/MCB.21.5.1874-1887.2001","article-title":"A Subset of Tumor-Derived Mutant Forms of p53 Down-Regulate p63 and p73 through a Direct Interaction with the p53 Core Domain","volume":"21","author":"Gaiddon","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.4161\/cc.7.21.6995","article-title":"The disruption of the protein complex mutantp53\/p73 increases selectively the response of tumor cells to anticancer drugs","volume":"7","author":"Cortese","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Schulz-Heddergott, R., and Moll, U.M. (2018). Gain-of-function (GOF) mutant p53 as actionable therapeutic target. Cancers, 10.","DOI":"10.3390\/cancers10060188"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Di Agostino, S. (2020). The impact of mutant p53 in the non-coding RNA world. Biomolecules, 10.","DOI":"10.3390\/biom10030472"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1038\/onc.2012.334","article-title":"Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis","volume":"32","author":"Dong","year":"2013","journal-title":"Oncogene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1038\/onc.2012.305","article-title":"Mutant p53 drives invasion in breast tumors through up-regulation of miR-155","volume":"32","author":"Neilsen","year":"2013","journal-title":"Oncogene"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/75586","article-title":"A common polymorphism acts as an intragenic modifier of mutant p53 behaviour","volume":"25","author":"Marin","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1535-6108(03)00079-5","article-title":"P53 Polymorphism Influences Response in Cancer Chemotherapy Via Modulation of P73-Dependent Apoptosis","volume":"3","author":"Bergamaschi","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S1535-6108(03)00078-3","article-title":"Chemosensitivity linked to p73 function","volume":"3","author":"Irwin","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1002\/1097-0142(19940615)73:12<3087::AID-CNCR2820731230>3.0.CO;2-9","article-title":"Low frequency of the p53 gene mutations in neuroblastoma","volume":"73","author":"Hosoi","year":"1994","journal-title":"Cancer"},{"key":"ref_73","first-page":"127","article-title":"Expression of p53 in human neuroblastoma- and neuroepithelioma-derived cell lines","volume":"7","author":"Davidoff","year":"1992","journal-title":"Oncogene"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/1096-911X(20001201)35:6<563::AID-MPO15>3.0.CO;2-J","article-title":"p53 Mutations and loss of p53 function confer multidrug resistance in neuroblastoma","volume":"35","author":"Keshelava","year":"2000","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_75","first-page":"6185","article-title":"Loss of p53 function confers high-level multidrug resistance in neuroblastoma cell lines","volume":"61","author":"Keshelava","year":"2001","journal-title":"Cancer Res."},{"key":"ref_76","first-page":"4053","article-title":"Mutation of the p53 Gene in Neuroblastoma and Its Relationship with N-myc Amplification","volume":"53","author":"Imamura","year":"1993","journal-title":"Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/(SICI)1096-911X(199709)29:3<206::AID-MPO7>3.0.CO;2-H","article-title":"Concomitant p53 mutation and MYCN amplification if neuroblastoma","volume":"29","author":"Manhani","year":"1997","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_78","first-page":"8","article-title":"Evidence for the Development of p53 Mutations after Cytotoxic Therapy in a Neuroblastoma Cell Line","volume":"61","author":"Tweddle","year":"2001","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1200\/JCO.1999.17.7.2264","article-title":"Molecular biology of neuroblastoma","volume":"17","author":"Maris","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6302","DOI":"10.1073\/pnas.0802091105","article-title":"Small-molecule RETRA suppresses mutant p53-bearing cancer cells through a p73-dependent salvage pathway","volume":"105","author":"Kravchenko","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.ccr.2014.01.021","article-title":"Mutant p53 in cancer: New functions and therapeutic opportunities","volume":"25","author":"Muller","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.canlet.2019.01.014","article-title":"New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma","volume":"446","author":"Gomes","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1101\/gad.1695308","article-title":"TAp73 knockout shows genomic instability with infertility and tumor suppressor functions","volume":"22","author":"Tomasini","year":"2008","journal-title":"Genes Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/sj.cdd.4400993","article-title":"Expression of \u0394Np73 is a molecular marker for adverse outcome in neuroblastoma patients","volume":"9","author":"Casciano","year":"2002","journal-title":"Cell Death Differ."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"429","DOI":"10.2217\/fon.09.176","article-title":"p53 family: Therapeutic targets in neuroblastoma","volume":"6","author":"Wolter","year":"2010","journal-title":"Futur. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0304-3835(03)00092-2","article-title":"Biological and clinical role of p73 in neuroblastoma","volume":"197","author":"Romani","year":"2003","journal-title":"Cancer Lett."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1177\/1947601911408890","article-title":"P73 in cancer","volume":"2","author":"Rufini","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/ijc.10618","article-title":"Frequent inactivation of the p73 gene by abnormal methylation or LOH in Non-Hodgkin\u2019s Lymphomas","volume":"102","author":"Melendez","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.1038\/sj.onc.1203807","article-title":"Methylation-independent silencing of the p73 gene in neuroblastoma","volume":"19","author":"Banelli","year":"2000","journal-title":"Oncogene"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1126\/science.289.5477.304","article-title":"An anti-apoptotic role for the p53 family member, p73, during developmental neuron death","volume":"289","author":"Pozniak","year":"2000","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1101\/gad.1873910","article-title":"Isoform-specific p73 knockout mice reveal a novel role for \u0394Np73 in the DNA damage response pathway","volume":"24","author":"Wilhelm","year":"2010","journal-title":"Genes Dev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/sj.cdd.4400992","article-title":"Role of methylation in the control of \u0394Np73 expression in neuroblastoma","volume":"9","author":"Casciano","year":"2002","journal-title":"Cell Death Differ."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/cdd.2008.60","article-title":"Itch: A HECT-type E3 ligase regulating immunity, skin and cancer","volume":"15","author":"Melino","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ccr.2008.06.001","article-title":"The HECT Family of E3 Ubiquitin Ligases: Multiple Players in Cancer Development","volume":"14","author":"Bernassola","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.bbrc.2007.06.104","article-title":"Itch inhibition regulates chemosensitivity in vitro","volume":"361","author":"Hansen","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"16926","DOI":"10.18632\/oncotarget.4700","article-title":"Anti-tumoral effect of desmethylclomipramine in lung cancer stem cells","volume":"6","author":"Giacobbe","year":"2015","journal-title":"Oncotarget"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.nano.2014.09.010","article-title":"A nano-enabled cancer-specific ITCH RNAi chemotherapy booster for pancreatic cancer","volume":"11","author":"Jones","year":"2015","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/s41598-020-57854-6","article-title":"Silencing E3 Ubiqutin ligase ITCH as a potential therapy to enhance chemotherapy efficacy in p53 mutant neuroblastoma cells","volume":"10","author":"Meng","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.semcancer.2020.03.003","article-title":"ITCH as a potential therapeutic target in human cancers","volume":"67","author":"Yin","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.1128\/MCB.00101-14","article-title":"WWP2-WWP1 Ubiquitin Ligase Complex Coordinated by PPM1G Maintains the Balance between Cellular p73 and \u0394Np73 Levels","volume":"34","author":"Chaudhary","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1038\/onc.2009.177","article-title":"The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73","volume":"28","author":"Peschiaroli","year":"2009","journal-title":"Oncogene"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"12877","DOI":"10.1073\/pnas.0911828107","article-title":"Differential control of TAp73 and \u0394Np73 protein stability by the ring finger ubiquitin ligase PIR2","volume":"107","author":"Sayan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/sj.emboj.7600444","article-title":"The ubiquitin-protein ligase Itch regulates p73 stability","volume":"24","author":"Rossi","year":"2005","journal-title":"EMBO J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e1203","DOI":"10.1038\/cddis.2014.113","article-title":"High throughput screening for inhibitors of the HECT ubiquitin E3 ligase ITCH identifies antidepressant drugs as regulators of autophagy","volume":"5","author":"Rossi","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/sj.bjp.0707253","article-title":"Tricyclic antidepressant pharmacology and therapeutic drug interactions updated","volume":"151","author":"Gillman","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s12276-021-00635-6","article-title":"Aurora kinase A, a synthetic lethal target for precision cancer medicine","volume":"53","author":"Mou","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12935-019-1072-y","article-title":"Silencing of AURKA augments the antitumor efficacy of the AURKA inhibitor MLN8237 on neuroblastoma cells","volume":"20","author":"Yang","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/onc.2014.14","article-title":"The aurora kinases in cell cycle and leukemia","volume":"34","author":"Goldenson","year":"2015","journal-title":"Oncogene"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00018-012-1073-7","article-title":"Aurora A kinase (AURKA) in normal and pathological cell division","volume":"70","author":"Nikonova","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3389\/fonc.2016.00247","article-title":"Functional significance of Aurora kinases-p53 protein family interactions in cancer","volume":"6","author":"Sasai","year":"2016","journal-title":"Front. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1046\/j.1365-2443.2002.00592.x","article-title":"Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells","volume":"7","author":"Marumoto","year":"2002","journal-title":"Genes Cells"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"28943","DOI":"10.1074\/jbc.M600235200","article-title":"Gadd45a interacts with aurora-A and inhibits its kinase activity","volume":"281","author":"Shao","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nature03155","article-title":"Fbxw7\/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene","volume":"432","author":"Mao","year":"2004","journal-title":"Nature"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.4161\/cc.21732","article-title":"p53 negatively regulates Aurora A via both transcriptional and posttranslational regulation","volume":"11","author":"Wu","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.4161\/cc.22381","article-title":"FBXW7 is involved in Aurora B degradation","volume":"11","author":"Teng","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1158\/1541-7786.MCR-12-0025","article-title":"Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development","volume":"10","author":"Kwon","year":"2012","journal-title":"Mol. Cancer Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ccr.2006.11.025","article-title":"Crosstalk between Aurora-A and p53: Frequent Deletion or Downregulation of Aurora-A in Tumors from p53 Null Mice","volume":"11","author":"Mao","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ccr.2008.12.005","article-title":"Stabilization of N-Myc Is a Critical Function of Aurora A in Human Neuroblastoma","volume":"15","author":"Otto","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ccr.2013.05.005","article-title":"Small Molecule Inhibitors of Aurora-A Induce Proteasomal Degradation of N-Myc in Childhood Neuroblastoma","volume":"24","author":"Brockmann","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/ng1279","article-title":"Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53","volume":"36","author":"Katayama","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"52175","DOI":"10.1074\/jbc.M406802200","article-title":"Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215","volume":"279","author":"Liu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"8998","DOI":"10.1158\/0008-5472.CAN-08-2658","article-title":"Aurora kinase A inhibition leads to p73-dependent apoptosis in p53-deficient cancer cells","volume":"68","author":"Dar","year":"2008","journal-title":"Cancer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ccr.2011.12.025","article-title":"Aurora Kinase-A Inactivates DNA Damage-Induced Apoptosis and Spindle Assembly Checkpoint Response Functions of p73","volume":"21","author":"Katayama","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"636","DOI":"10.4161\/cbt.8.7.7929","article-title":"hBub1 negatively regulates p53 mediated early cell death upon mitotic checkpoint activation","volume":"8","author":"Gao","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nature04217","article-title":"Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells","volume":"437","author":"Fujiwara","year":"2005","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jcb.10411","article-title":"G1 tetraploidy checkpoint and the suppression of tumorigenesis","volume":"88","author":"Margolis","year":"2003","journal-title":"J. Cell. Biochem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1091\/mbc.12.5.1315","article-title":"Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1","volume":"12","author":"Andreassen","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1073\/pnas.0812096106","article-title":"TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity","volume":"106","author":"Tomasini","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"421","DOI":"10.4161\/cc.8.3.7623","article-title":"TAp73\u03b1 binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy","volume":"8","author":"Vernole","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.ejca.2008.09.024","article-title":"The expression of the \u0394Np73\u03b2 isoform of p73 leads to tetraploidy","volume":"45","author":"Marrazzo","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.neo.2021.05.003","article-title":"The synergy of BET inhibitors with aurora A kinase inhibitors in MYCN-amplified neuroblastoma is heightened with functional TP53","volume":"23","author":"Yi","year":"2021","journal-title":"Neoplasia"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"100776","DOI":"10.1016\/j.neo.2022.100776","article-title":"Combining selinexor with alisertib to target the p53 pathway in neuroblastoma","volume":"26","author":"Nguyen","year":"2022","journal-title":"Neoplasia"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"4940","DOI":"10.1073\/pnas.81.15.4940","article-title":"Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma","volume":"81","author":"Schwab","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0092-8674(83)90169-1","article-title":"Transposition and amplification of oncogene-related sequences in human neuroblastomas","volume":"35","author":"Kohl","year":"1983","journal-title":"Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s00595-019-01790-0","article-title":"The roles played by the MYCN, Trk, and ALK genes in neuroblastoma and neural development","volume":"49","author":"Higashi","year":"2019","journal-title":"Surg. Today"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1242\/dev.124.10.1953","article-title":"Regulation of the neural crest cell fate by N-myc: Promotion of ventral migration and neuronal differentiation","volume":"124","author":"Wakamatsu","year":"1997","journal-title":"Development"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature05953","article-title":"Non-transcriptional control of DNA replication by c-Myc","volume":"448","author":"Ying","year":"2007","journal-title":"Nature"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nature03043","article-title":"MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer","volume":"431","author":"Shachaf","year":"2004","journal-title":"Nature"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1126\/science.1071489","article-title":"Sustained loss of a neoplastic phenotype by brief inactivation of MYC","volume":"297","author":"Jain","year":"2002","journal-title":"Science"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/0006-291X(89)90771-7","article-title":"Transrepression of the N-MYC expression by C-MYC protein","volume":"162","author":"Kubota","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_141","first-page":"7942","article-title":"Complementation by wild-type p53 of interleukin-6 effects on M1 cells: Induction of cell cycle exit and cooperativity with c-myc suppression","volume":"13","author":"Levy","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"7423","DOI":"10.1128\/MCB.25.17.7423-7431.2005","article-title":"p53-Dependent Transcriptional Repression of c-myc Is Required for G1 Cell Cycle Arrest","volume":"25","author":"Ho","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4980","DOI":"10.1038\/s41467-020-18735-8","article-title":"c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis","volume":"11","author":"Feng","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"15113","DOI":"10.1074\/jbc.M111281200","article-title":"Physical interaction of p73 with c-Myc and MM1, a c-Myc-binding protein, and modulation of the p73 function","volume":"277","author":"Watanabe","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3389\/fonc.2012.00173","article-title":"p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance","volume":"2","author":"Chen","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1101\/gad.12.15.2424","article-title":"Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization","volume":"12","author":"Zindy","year":"1998","journal-title":"Genes Dev."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"624079","DOI":"10.3389\/fonc.2020.624079","article-title":"MYCN Function in Neuroblastoma Development","volume":"10","author":"Otte","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12035-021-02584-7","article-title":"Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis","volume":"59","author":"Chen","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1101\/gad.1021202","article-title":"N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation","volume":"16","author":"Knoepfler","year":"2002","journal-title":"Genes Dev."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"856","DOI":"10.2353\/ajpath.2009.090019","article-title":"MYCN promotes the expansion of Phox2B-positive neuronal progenitors to drive neuroblastoma development","volume":"175","author":"Alam","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"38498","DOI":"10.1074\/jbc.M111.276675","article-title":"Differential Regulation of N-Myc and c-Myc Synthesis, Degradation, and Transcriptional Activity by the Ras\/Mitogen-activated Protein Kinase Pathway","volume":"286","author":"Kapeli","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1056\/NEJMra0804577","article-title":"Recent Advances in Neuroblastoma","volume":"362","author":"Maris","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"a014415","DOI":"10.1101\/cshperspect.a014415","article-title":"Neuroblastoma and MYCN","volume":"3","author":"Huang","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/305245a0","article-title":"Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour","volume":"305","author":"Schwab","year":"1983","journal-title":"Nature"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1056\/NEJM198510313131802","article-title":"Association of multiple copies of the N-MYC oncogene with rapid progression of neuroblastomas","volume":"313","author":"Seeger","year":"1985","journal-title":"N. Engl. J. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1126\/science.6719137","article-title":"Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage","volume":"224","author":"Brodeur","year":"1984","journal-title":"Science"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1093\/emboj\/16.11.2985","article-title":"Targeted expression of MYCN causes neuroblastoma in transgenic mice","volume":"16","author":"Weiss","year":"1997","journal-title":"EMBO J."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"3357","DOI":"10.1038\/onc.2014.269","article-title":"A Cre-conditional MYCN -driven neuroblastoma mouse model as an improved tool for preclinical studies","volume":"34","author":"Althoff","year":"2015","journal-title":"Oncogene"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"5075","DOI":"10.1038\/onc.2017.128","article-title":"MYCN induces neuroblastoma in primary neural crest cells","volume":"36","author":"Olsen","year":"2017","journal-title":"Oncogene"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ccr.2012.02.010","article-title":"Article Activated ALK Collaborates with MYCN in Neuroblastoma Pathogenesis","volume":"21","author":"Zhu","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nature18632","article-title":"Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma","volume":"535","author":"Powers","year":"2016","journal-title":"Nature"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1126\/science.1154040","article-title":"Selective Blockade of MicroRNA Processing by Lin28","volume":"320","author":"Viswanathan","year":"2008","journal-title":"Science"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1158\/2159-8290.CD-17-0273","article-title":"The Expanding World of N-MYC\u2013Driven Tumors","volume":"8","author":"Rickman","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1242\/dev.02189","article-title":"Target-dependent specification of the neurotransmitter phenotype: Cholinergic differentiation of sympathetic neurons is mediated in vivo by gp130 signaling","volume":"133","author":"Stanke","year":"2006","journal-title":"Development"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/ng.2436","article-title":"LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression","volume":"44","author":"Molenaar","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ccr.2014.06.018","article-title":"Article Lin28b Is Sufficient to Drive Liver Cancer and Necessary for Its Maintenance in Murine Models","volume":"26","author":"Nguyen","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1101\/gad.237149.113","article-title":"Lin28 sustains early renal progenitors and induces Wilms tumor","volume":"28","author":"Urbach","year":"2014","journal-title":"Genes Dev."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1038\/onc.2011.343","article-title":"MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells","volume":"31","author":"Gu","year":"2012","journal-title":"Oncogene"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.4161\/cc.10.17.17118","article-title":"Crosstalk between MYCN and MDM2-p53 signal pathways regulates tumor cell growth and apoptosis in neuroblastoma","volume":"10","author":"He","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1073\/pnas.0405495102","article-title":"The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma","volume":"102","author":"Slack","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"20323","DOI":"10.18632\/oncotarget.24859","article-title":"MYCN acts as a direct co-regulator of p53 in MYCN amplified neuroblastoma","volume":"9","author":"Agarwal","year":"2018","journal-title":"Oncotarget"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.1093\/nar\/gkn394","article-title":"p73\u03b1 isoforms drive opposite transcriptional and post-transcriptional regulation of MYCN expression in neuroblastoma cells","volume":"36","author":"Horvilleur","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"623679","DOI":"10.3389\/fonc.2020.623679","article-title":"Targeting MYCN in Pediatric and Adult Cancers","volume":"10","author":"Liu","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1124\/jpet.110.170555","article-title":"In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc\/Max dimerization","volume":"335","author":"Clausen","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.phrs.2018.02.023","article-title":"Molecular mechanisms and therapeutic targets in neuroblastoma","volume":"131","author":"Johnsen","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1200\/JCO.2015.65.4889","article-title":"Phase I study of the Aurora A kinase inhibitor Alisertib in combination with irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma: A NANT (new approaches to neuroblastoma therapy) trial","volume":"34","author":"DuBois","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1002\/med.21750","article-title":"Molecular targeting therapies for neuroblastoma: Progress and challenges","volume":"41","author":"Zafar","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.molonc.2015.11.005","article-title":"Novel pharmacodynamic biomarkers for MYCN protein and PI3K\/AKT\/mTOR pathway signaling in children with neuroblastoma","volume":"10","author":"Smith","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.soc.2013.06.008","article-title":"Targeting the PI3-kinase\/Akt\/mTOR Signaling Pathway","volume":"22","author":"Hassan","year":"2013","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.1002\/jcp.27486","article-title":"An overview of microRNAs: Biology, functions, therapeutics, and analysis methods","volume":"234","author":"Saliminejad","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1261\/rna.2183803","article-title":"A uniform system for microRNA annotation","volume":"9","author":"Ambros","year":"2003","journal-title":"RNA"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1208\/s12248-010-9194-0","article-title":"MicroRNA and cancer","volume":"12","author":"Li","year":"2010","journal-title":"AAPS J."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1177\/0300985813502820","article-title":"MicroRNAs: History, Biogenesis, and Their Evolving Role in Animal Development and Disease","volume":"51","author":"Bhaskaran","year":"2014","journal-title":"Vet. Pathol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/nar\/gkj112","article-title":"miRBase: microRNA sequences, targets and gene nomenclature","volume":"34","author":"Grocock","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_185","first-page":"154","article-title":"miRBase: Tools for microRNA genomics","volume":"36","author":"Saini","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Syeda, Z.A., Langden, S.S.S., Munkhzul, C., Lee, M., and Song, S.J. (2020). Regulatory mechanism of microrna expression in cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051723"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Pajares, M.J., Alemany-cosme, E., Go\u00f1i, S., Bandres, E., Palanca-Ballester, C., and Sandoval, J. (2021). Epigenetic regulation of microRNAs in cancer: Shortening the distance from bench to bedside. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147350"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-1-4939-8982-9_2","article-title":"p73-Governed miRNA Networks: Translating Bioinformatics Approaches to Therapeutic Solutions for Cancer Metastasis","volume":"Volume 1912","author":"Lai","year":"2019","journal-title":"Computational Biology of Non-Coding RNA: Methods and Protocols"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jcb.25609","article-title":"MicroRNA Control of p53","volume":"118","author":"Liu","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Veeraraghavan, V.P., Jayaraman, S., Rengasamy, G., Mony, U., Ganapathy, D.M., Geetha, R.V., and Sekar, D. (2022). Deciphering the role of micrornas in neuroblastoma. Molecules, 27.","DOI":"10.3390\/molecules27010099"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"584","DOI":"10.2174\/0929867324666171003120335","article-title":"MicroRNAs in Neuroblastoma: Biomarkers with Therapeutic Potential","volume":"25","author":"Galardi","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Tivnan, A., Orr, W.S., Gubala, V., Nooney, R., Williams, D.E., McDonagh, C., Prenter, S., Harvey, H., Domingo-Fern\u00e1ndez, R., and Bray, I.M. (2012). Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038129"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"e10615","DOI":"10.1371\/journal.pone.0010615","article-title":"The Tumor Suppressors p53, p63, and p73 Are Regulators of MicroRNA Processing Complex","volume":"5","author":"Boominathan","year":"2010","journal-title":"PLoS ONE"},{"key":"ref_194","first-page":"1","article-title":"Tumor suppressors p53, p63, and p73 inhibit migrating cancer stem cells by increasing the expression of stem cell suppressing miRNAs","volume":"1","author":"Boominathan","year":"2010","journal-title":"Cell"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"695723","DOI":"10.3389\/fcell.2021.695723","article-title":"Regulation of miRNAs Expression by Mutant p53 Gain of Function in Cancer","volume":"9","author":"Madrigal","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1016\/j.febslet.2014.03.054","article-title":"Mutant p53 exerts oncogenic effects through microRNAs and their target gene networks","volume":"588","author":"Li","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/febs.12074","article-title":"MicroRNA-15a promotes neuroblastoma migration by targeting reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and regulating matrix metalloproteinase-9 expression","volume":"280","author":"Chen","year":"2013","journal-title":"FEBS J."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.3892\/ol.2017.6052","article-title":"Reduction of miR-21 induces SK-N-SH cell apoptosis and inhibits proliferation via PTEN\/PDCD4","volume":"13","author":"Wang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"839","DOI":"10.3892\/ol.2014.1794","article-title":"MicroRNA-23a promotes neuroblastoma cell metastasis by targeting CDH1","volume":"7","author":"Cheng","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1158\/1078-0432.CCR-16-1591","article-title":"microRNA-221 enhances MYCN via targeting nemo-like kinase and functions as an oncogene related to poor prognosis in neuroblastoma","volume":"23","author":"He","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/nm.2227","article-title":"miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN amplified neuroblastoma","volume":"16","author":"Swarbrick","year":"2011","journal-title":"Nat. Med."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1093\/hmg\/ddv018","article-title":"miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase","volume":"24","author":"Qu","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.biopha.2016.07.010","article-title":"miR-1303 promotes the proliferation of neuroblastoma cell SH-SY5Y by targeting GSK3\u03b2 and SFRP1","volume":"83","author":"Li","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_204","first-page":"3729","article-title":"Downregulation of microRNA-3934-5p induces apoptosis and inhibits the proliferation of neuroblastoma cells by targeting TP53INP1","volume":"18","author":"Ye","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1158\/1535-7163.MCT-12-0001","article-title":"MicroRNA-9 targets matrix metalloproteinase 14 to inhibit invasion, metastasis, and angiogenesis of neuroblastoma cells","volume":"11","author":"Zhang","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/1878-0261.12588","article-title":"miR-15a-5p, miR-15b-5p, and miR-16-5p inhibit tumor progression by directly targeting MYCN in neuroblastoma","volume":"14","author":"Chava","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1074\/mcp.M113.035808","article-title":"Early targets of miR-34a in neuroblastoma","volume":"13","author":"Carotenuto","year":"2014","journal-title":"Mol. Cell. Proteom."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"21093","DOI":"10.1073\/pnas.1112061109","article-title":"Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets","volume":"108","author":"Agostini","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"e78713","DOI":"10.1371\/journal.pone.0078713","article-title":"miR-192 directly binds and regulates Dicer1 expression in neuroblastoma","volume":"8","author":"Guedj","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"5554","DOI":"10.3892\/mmr.2015.4013","article-title":"MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68","volume":"12","author":"Zhao","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1016\/j.febslet.2013.09.044","article-title":"miR-338-3p suppresses neuroblastoma proliferation invasion and migration through targeting PREX2a","volume":"587","author":"Chen","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40659-018-0162-y","article-title":"MicroRNA-1247 inhibits cell proliferation by directly targeting ZNF346 in childhood neuroblastoma","volume":"51","author":"Wu","year":"2018","journal-title":"Biol. Res."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/cdd.2010.164","article-title":"MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival","volume":"18","author":"Afanasyeva","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"e1081","DOI":"10.1038\/cddis.2014.42","article-title":"MYCN gene expression is required for the onset of the differentiation programme in neuroblastoma cells","volume":"5","author":"Guglielmi","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"e3100","DOI":"10.1038\/cddis.2017.495","article-title":"Alternative mechanisms of MIR-34a regulation in cancer","volume":"8","author":"Culig","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"9027","DOI":"10.1038\/srep09027","article-title":"Genome wide expression profiling of p53 regulated miRNAs in neuroblastoma","volume":"5","author":"Rihani","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1101\/gad.1767609","article-title":"MicroRNA-125b is a novel negative regulator of p53","volume":"23","author":"Le","year":"2009","journal-title":"Genes Dev."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.3892\/or.2017.5983","article-title":"MiR-504 promotes tumour growth and metastasis in human osteosarcoma by targeting TP53INP1","volume":"38","author":"Cai","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1200\/JCO.21.00278","article-title":"Revised Neuroblastoma Risk Classification System: A Report From the Children\u2019s Oncology Group","volume":"39","author":"Irwin","year":"2021","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/24\/6212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:30Z","timestamp":1760146950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/24\/6212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":219,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["cancers14246212"],"URL":"https:\/\/doi.org\/10.3390\/cancers14246212","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,16]]}}}