{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:00Z","timestamp":1787027820524,"version":"build-2736575974"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes for Health Research","award":["451405"],"award-info":[{"award-number":["451405"]}]},{"name":"London Health Sciences Foundation through donations","award":["451405"],"award-info":[{"award-number":["451405"]}]},{"name":"the Karen Pooley Scholarship in Ovarian Cancer Research with funds from the London Health Sciences Foundation","award":["451405"],"award-info":[{"award-number":["451405"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Epithelial ovarian cancer (EOC) exhibits a unique mode of metastasis, involving spheroid formation in the peritoneum. Our research on EOC spheroid cell biology has provided valuable insights into the signaling plasticity associated with metastasis. We speculate that EOC cells modify their biology between tumour and spheroid states during cancer dormancy, although the specific mechanisms underlying this transition remain unknown. Here, we present novel findings from direct comparisons between cultured EOC spheroids and organoids. Our results indicated that AMP-activated protein kinase (AMPK) activity was significantly upregulated and protein kinase B (Akt) was downregulated in EOC spheroids compared to organoids, suggesting a clear differential phenotype. Through RNA sequencing analysis, we further supported these phenotypic differences and highlighted the significance of cell cycle regulation in organoids. By inhibiting the G2\/M checkpoint via kinase inhibitors, we confirmed that this pathway is essential for organoids. Interestingly, our results suggest that specifically targeting aurora kinase A (AURKA) may represent a promising therapeutic strategy since our cells were equally sensitive to Alisertib treatment as both spheroids and organoids. Our findings emphasize the importance of studying cellular adaptations of EOC cells, as there may be different therapeutic targets depending on the step of EOC disease progression.<\/jats:p>","DOI":"10.3390\/cells14020133","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T10:27:58Z","timestamp":1737109678000},"page":"133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploiting Cancer Dormancy Signaling Mechanisms in Epithelial Ovarian Cancer Through Spheroid and Organoid Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Emily J.","family":"Tomas","sequence":"first","affiliation":[{"name":"The Mary and John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 5W9, Canada"},{"name":"Department of Anatomy & Cell Biology, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudith Ramos","family":"Valdes","sequence":"additional","affiliation":[{"name":"The Mary and John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Davis","sequence":"additional","affiliation":[{"name":"The Mary and John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0607-5858","authenticated-orcid":false,"given":"Bart","family":"Kolendowski","sequence":"additional","affiliation":[{"name":"The Mary and John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Buensuceso","sequence":"additional","affiliation":[{"name":"The Mary and John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2796-9941","authenticated-orcid":false,"given":"Gabriel E.","family":"DiMattia","sequence":"additional","affiliation":[{"name":"The Mary and John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 5W9, Canada"},{"name":"Department of Oncology, Western University, London, ON N6A 5C1, Canada"},{"name":"Department of Biochemistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-8066","authenticated-orcid":false,"given":"Trevor G.","family":"Shepherd","sequence":"additional","affiliation":[{"name":"The Mary and John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 5W9, Canada"},{"name":"Department of Anatomy & Cell Biology, Western University, London, ON N6A 5C1, Canada"},{"name":"Department of Oncology, Western University, London, ON N6A 5C1, Canada"},{"name":"Department of Obstetrics & Gynaecology, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/S0140-6736(18)32552-2","article-title":"Epithelial Ovarian Cancer","volume":"393","author":"Lheureux","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/s41467-017-00962-1","article-title":"High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube","volume":"8","author":"Papp","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7547","DOI":"10.1073\/pnas.1017300108","article-title":"Modeling High-Grade Serous Ovarian Carcinogenesis from the Fallopian Tube","volume":"108","author":"Karst","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107502","DOI":"10.1016\/j.celrep.2020.03.066","article-title":"Molecular Analysis of Clinically Defined Subsets of High-Grade Serous Ovarian Cancer","volume":"31","author":"Lee","year":"2020","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/s41591-020-0926-0","article-title":"A Single-Cell Landscape of High-Grade Serous Ovarian Cancer","volume":"26","author":"Izar","year":"2020","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.2353\/ajpath.2010.100105","article-title":"Ovarian Cancer Development and Metastasis","volume":"177","author":"Lengyel","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Goyeneche, A., Lisio, M.A., Fu, L., Srinivasan, R., Capuccino, J.V., Gao, Z.H., and Telleria, C. (2020). The Capacity of High-Grade Serous Ovarian Cancer Cells to Form Multicellular Structures Spontaneously along Disease Progression Correlates with Their Orthotopic Tumorigenicity in Immunosuppressed Mice. Cancers, 12.","DOI":"10.3390\/cancers12030699"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Das, T., Meunier, L., Barbe, L., Provencher, D., Guenat, O., Gervais, T., and Mes-Masson, A.M. (2013). Empirical Chemosensitivity Testing in a Spheroid Model of Ovarian Cancer Using a Microfluidics-Based Multiplex Platform. Biomicrofluidics, 7.","DOI":"10.1063\/1.4774309"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ygyno.2015.04.014","article-title":"Formation of Stable Small Cell Number Three-Dimensional Ovarian Cancer Spheroids Using Hanging Drop Arrays for Preclinical Drug Sensitivity Assays","volume":"138","author":"Raghavan","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Liao, J., Qian, F., Tchabo, N., Mhawech-Fauceglia, P., Beck, A., Qian, Z., Wang, X., Huss, W.J., Lele, S.B., and Morrison, C.D. (2014). Ovarian Cancer Spheroid Cells with Stem Cell-like Properties Contribute to Tumor Generation, Metastasis and Chemotherapy Resistance through Hypoxia-Resistant Metabolism. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0084941"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dean, M., Jin, V., Bergsten, T.M., Austin, J.R., Lantvit, D.D., Russo, A., and Burdette, J.E. (2019). Loss of PTEN in Fallopian Tube Epithelium Results in Multicellular Tumor Spheroid Formation and Metastasis to the Ovary. Cancers, 11.","DOI":"10.3390\/cancers11060884"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"a037556","DOI":"10.1101\/cshperspect.a037556","article-title":"Cancer Cell Dormancy in Metastasis","volume":"10","author":"Summers","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13008-022-00079-y","article-title":"Principles of Dormancy Evident in High-Grade Serous Ovarian Cancer","volume":"17","author":"Shepherd","year":"2022","journal-title":"Cell Div."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13048-023-01145-x","article-title":"Insights into High-Grade Serous Carcinoma Pathobiology Using Three-Dimensional Culture Model Systems","volume":"16","author":"Tomas","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1002\/ijc.24188","article-title":"Compact Spheroid Formation by Ovarian Cancer Cells Is Associated with Contractile Behavior and an Invasive Phenotype","volume":"124","author":"Sodek","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1158\/1541-7786.MCR-16-0323-T","article-title":"A Systematic Analysis of Negative Growth Control Implicates the DREAM Complex in Cancer Cell Dormancy","volume":"15","author":"MacDonald","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22424","DOI":"10.18632\/oncotarget.4211","article-title":"Intact LKB1 Activity Is Required for Survival of Dormant Ovarian Cancer Spheroids","volume":"6","author":"Peart","year":"2015","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13048-020-00660-5","article-title":"Activated CAMKK\u03b2-AMPK Signaling Promotes Autophagy in a Spheroid Model of Ovarian Tumour Metastasis","volume":"13","author":"Laski","year":"2020","journal-title":"J. Ovarian Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1158\/2159-8274.CD-11-0010","article-title":"Ovarian Cancer Spheroids Use Myosin-Generated Force to Clear the Mesothelium","volume":"1","author":"Iwanicki","year":"2011","journal-title":"Cancer Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1593\/neo.07472","article-title":"Characterization of Ovarian Cancer Ascites on Cell Invasion, Proliferation, Spheroid Formation, and Gene Expression in an in Vitro Model of Epithelial Ovarian Cancer","volume":"9","author":"Puiffe","year":"2007","journal-title":"Neoplasia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e142677","DOI":"10.1172\/JCI142677","article-title":"Inhibition of Relaxin Autocrine Signaling Confers Therapeutic Vulnerability in Ovarian Cancer","volume":"131","author":"Burston","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1158\/1541-7786.MCR-19-0530","article-title":"AMPK-Independent LKB1 Activity Is Required for Efficient Epithelial Ovarian Cancer Metastasis","volume":"18","author":"Buensuceso","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1042\/BCJ20170458","article-title":"Phosphorylation of AMPK by Upstream Kinases Is Required for Activity in Mammalian Cells","volume":"474","author":"Willows","year":"2017","journal-title":"Biochem. J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Endo, H., Owada, S., Inagaki, Y., Shida, Y., and Tatemichi, M. (2018). Glucose Starvation Induces LKB1-AMPK-Mediated MMP-9 Expression in Cancer Cells. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-28074-w"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1093\/carcin\/bgu049","article-title":"Combination of AKT Inhibition with Autophagy Blockade Effectively Reduces Ascites-Derived Ovarian Cancer Cell Viability","volume":"35","author":"Correa","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1038\/s41467-020-16432-0","article-title":"Assessing the Origin of High-Grade Serous Ovarian Cancer Using CRISPR-Modification of Mouse Organoids","volume":"11","author":"Kopper","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107762","DOI":"10.1016\/j.celrep.2020.107762","article-title":"Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses","volume":"31","author":"Hami","year":"2020","journal-title":"Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/s41591-019-0422-6","article-title":"An Organoid Platform for Ovarian Cancer Captures Intra- and Interpatient Heterogeneity","volume":"25","author":"Kopper","year":"2019","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Filippou, P.S., Aleman, J., Garreta, E., Wang, Y., Yang, J., Huang, S., Cheng, S., Jin, Y., and Zhang, N. (2021). Application of Ovarian Cancer Organoids in Precision Medicine: Key Challenges and Current Opportunities. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.701429"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13046-021-01917-7","article-title":"Patient-Derived Organoids and High Grade Serous Ovarian Cancer: From Disease Modeling to Personalized Medicine","volume":"40","author":"Nero","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yee, C., Dickson, K.-A., Muntasir, M.N., Ma, Y., and Marsh, D.J. (2022). Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.836984"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Senkowski, W., Gall-Mas, L., Marin Falco, M., Li, Y., Lavikka, K., Kriegbaum, M.C., Oikkonen, J., Bulanova, D., Pietras, E.J., and Vo\u00dfgr\u00f6ne, K. (2023). A Platform for Efficient Establishment, Expansion and Drug Response Profiling of High-Grade Serous Ovarian Cancer Organoids. Dev. Cell.","DOI":"10.1101\/2022.04.21.489027"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gorski, J.W., Zhang, Z., McCorkle, J.R., DeJohn, J.M., Wang, C., Miller, R.W., Gallion, H.H., Dietrich, C.S., Ueland, F.R., and Kolesar, J.M. (2021). Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081021"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1186\/s13046-021-02139-7","article-title":"The Role of Patient-Derived Ovarian Cancer Organoids in the Study of PARP Inhibitors Sensitivity and Resistance: From Genomic Analysis to Functional Testing","volume":"40","author":"Tao","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"106232","DOI":"10.1016\/j.phrs.2022.106232","article-title":"Developing Patient-Derived Organoids to Predict PARP Inhibitor Response and Explore Resistance Overcoming Strategies in Ovarian Cancer","volume":"179","author":"Tao","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nanki, Y., Chiyoda, T., Hirasawa, A., Ookubo, A., Itoh, M., Ueno, M., Akahane, T., Kameyama, K., Yamagami, W., and Kataoka, F. (2020). Patient-Derived Ovarian Cancer Organoids Capture the Genomic Profiles of Primary Tumours Applicable for Drug Sensitivity and Resistance Testing. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-69488-9"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Phan, N., Hong, J.J., Tofig, B., Mapua, M., Elashoff, D., Moatamed, N.A., Huang, J., Memarzadeh, S., Damoiseaux, R., and Soragni, A. (2019). A Simple High-Throughput Approach Identifies Actionable Drug Sensitivities in Patient-Derived Tumor Organoids. Commun. Biol., 2.","DOI":"10.1038\/s42003-019-0305-x"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/humu.22556","article-title":"Analysis of TP53 Mutation Status in Human Cancer Cell Lines: A Reassessment","volume":"35","author":"Leroy","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_39","first-page":"1384","article-title":"Inhibiting ULK1 Kinase Decreases Autophagy and Cell Viability in High-Grade Serous Ovarian Cancer Spheroids","volume":"10","author":"Singha","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.stemcr.2020.03.004","article-title":"Developing Organoids from Ovarian Cancer as Experimental and Preclinical Models","volume":"14","author":"Maenhoudt","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ygyno.2003.12.034","article-title":"Ovarian Carcinoma Ascites Spheroids Adhere to Extracellular Matrix Components and Mesothelial Cell Monolayers","volume":"93","author":"Burleson","year":"2004","journal-title":"Gynecol. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1757-2215-7-70","article-title":"Versican Regulates Metastasis of Epithelial Ovarian Carcinoma Cells and Spheroids","volume":"7","author":"Desjardins","year":"2014","journal-title":"J. Ovarian Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s10585-011-9451-3","article-title":"BMP Signalling Controls the Malignant Potential of Ascites-Derived Human Epithelial Ovarian Cancer Spheroids via AKT Kinase Activation","volume":"29","author":"Peart","year":"2012","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1530\/ERC-15-0383","article-title":"TGF\u03b2 Signaling Regulates Epithelial-Mesenchymal Plasticity in Ovarian Cancer Ascites-Derived Spheroids","volume":"23","author":"Rafehi","year":"2016","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"167312","DOI":"10.1016\/j.bbadis.2024.167312","article-title":"Metabolic Adaptation in Epithelial Ovarian Cancer Metastasis","volume":"1870","author":"Frederick","year":"2024","journal-title":"BBA-Mol. Basis Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1038\/s41388-019-1097-7","article-title":"Context-Dependent Activation of SIRT3 Is Necessary for Anchorage-Independent Survival and Metastasis of Ovarian Cancer Cells","volume":"39","author":"Kim","year":"2020","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Chuang, T.C., Shao, W.S., Hsu, S.C., Lee, S.L., Kao, M.C., and Wang, V. (2023). Baicalein Induces G2\/M Cell Cycle Arrest Associated with ROS Generation and CHK2 Activation in Highly Invasive Human Ovarian Cancer Cells. Molecules, 28.","DOI":"10.3390\/molecules28031039"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1007\/s13277-015-4770-7","article-title":"E2F1: A Promising Regulator in Ovarian Carcinoma","volume":"37","author":"Zhan","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Zhang, F., He, Z., and Zuo, M.Z. (2019). E2F2\/5\/8 Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00161"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lynch, K.N., Liu, J.F., Kesten, N., Chow, K.H., Shetty, A., He, R., Afreen, M.F., Yuan, L., Matulonis, U.A., and Growdon, W.B. (2021). Enhanced Efficacy of Aurora Kinase Inhibitors in G2\/m Checkpoint Deficient Tp53 Mutant Uterine Carcinomas Is Linked to the Summation of Lkb1\u2013Akt\u2013P53 Interactions. Cancers, 13.","DOI":"10.3390\/cancers13092195"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e161544","DOI":"10.1172\/JCI161544","article-title":"ODF2L Acts as a Synthetic Lethal Partner with WEE1 Inhibition in Epithelial Ovarian Cancer Models","volume":"133","author":"Li","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Roering, P., Siddiqui, A., Heuser, V.D., Potdar, S., Mikkonen, P., Oikkonen, J., Li, Y., Pikkusaari, S., Wennerberg, K., and Hynninen, J. (2022). Effects of Wee1 Inhibitor Adavosertib on Patient-Derived High-Grade Serous Ovarian Cancer Cells Are Multiple and Independent of Homologous Recombination Status. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.954430"},{"key":"ref_53","first-page":"425","article-title":"Alisertib, an Aurora Kinase A Inhibitor, Induces Apoptosis and Autophagy but Inhibits Epithelial to Mesenchymal Transition in Human Epithelial Ovarian Cancer Cells","volume":"9","author":"Ding","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gasimli, K., Raab, M., Tahmasbi Rad, M., Kurunci-Csacsko, E., Becker, S., Strebhardt, K., and Sanhaji, M. (2022). Sequential Targeting of PLK1 and PARP1 Reverses the Resistance to PARP Inhibitors and Enhances Platin-Based Chemotherapy in BRCA-Deficient High-Grade Serous Ovarian Cancer with KRAS Amplification. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810892"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Borah, N.A., and Reddy, M.M. (2021). Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer. Molecules, 26.","DOI":"10.3390\/molecules26071981"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1136\/ijgc-2020-001277","article-title":"Exploiting Replicative Stress in Gynecological Cancers as a Therapeutic Strategy","volume":"30","author":"Ngoi","year":"2020","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/GCO.0000000000000340","article-title":"Pathogenesis and Heterogeneity of Ovarian Cancer","volume":"29","author":"Kroeger","year":"2017","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1093\/carcin\/bgr140","article-title":"Modelling Genetic and Clinical Heterogeneity in Epithelial Ovarian Cancers","volume":"32","author":"Lawrenson","year":"2011","journal-title":"Carcinogenesis"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1158\/0008-5472.CAN-20-0521","article-title":"Multiomic Analysis of Subtype Evolution and Heterogeneity in High-Grade Serous Ovarian Carcinoma","volume":"80","author":"Geistlinger","year":"2021","journal-title":"Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.3892\/or.2015.4288","article-title":"Role of the LKB1\/AMPK Pathway in Tumor Invasion and Metastasis of Cancer Cells (Review)","volume":"34","author":"Li","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1083\/jcb.201610056","article-title":"Organoids: A Historical Perspective of Thinking in Three Dimensions","volume":"216","author":"Simian","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Brodeur, M.N., Simeone, K., Leclerc-Deslauniers, K., Fleury, H., Carmona, E., Provencher, D.M., and Mes-Masson, A.M. (2021). Carboplatin Response in Preclinical Models for Ovarian Cancer: Comparison of 2D Monolayers, Spheroids, Ex Vivo Tumors and in Vivo Models. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-97434-w"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s43046-022-00104-9","article-title":"Subtyping of High Grade Serous Ovarian Carcinoma: Histopathological and Immunohistochemical Approach","volume":"34","author":"Khashaba","year":"2022","journal-title":"J. Egypt. Natl. Cancer Inst."},{"key":"ref_64","first-page":"e174","article-title":"Comparison of the Value of PCNA and Ki-67 as Markers of Cell Proliferation in Ameloblastic Tumors","volume":"18","year":"2013","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41389-021-00329-8","article-title":"Dysregulated G2 Phase Checkpoint Recovery Pathway Reduces DNA Repair Efficiency and Increases Chromosomal Instability in a Wide Range of Tumours","volume":"10","author":"Fernando","year":"2021","journal-title":"Oncogenesis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"103112","DOI":"10.1016\/j.dnarep.2021.103112","article-title":"DNA Damage Response and PD-1\/PD-L1 Pathway in Ovarian Cancer","volume":"102","author":"Zhang","year":"2021","journal-title":"DNA Repair"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1080\/15384101.2021.1922806","article-title":"Targeting Cell Cycle Regulation via the G2-M Checkpoint for Synthetic Lethality in Melanoma","volume":"20","author":"Barnaba","year":"2021","journal-title":"Cell Cycle"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Chen, C.P., Yeh, C.N., Pan, Y.R., Huang, W.K., Hsiao, Y.T., Lo, C.H., and Wu, C.E. (2023). Wee1 Inhibition by MK1775 Potentiates Gemcitabine through Accumulated Replication Stress Leading to Apoptosis in Biliary Tract Cancer. Biomed. Pharmacother., 166.","DOI":"10.1016\/j.biopha.2023.115389"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Affatato, R., Carrassa, L., Chil\u00e0, R., Lupi, M., Restelli, V., and Damia, G. (2020). Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12030672"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e000718","DOI":"10.1136\/esmoopen-2020-000718","article-title":"Aurora Kinases in Ovarian Cancer","volume":"5","author":"Gambardella","year":"2020","journal-title":"ESMO Open"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ganapathi, R.N., Norris, E.J., Sutker, A.P., Klotz, K.E., and Ganapathi, M.K. (2020). Targeting Aurora A Kinase (AAK) in Platinum-Resistant High Grade Serous Ovarian Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01354"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7614","DOI":"10.1158\/1078-0432.CCR-11-1536","article-title":"Characterization of Alisertib (MLN8237), an Investigational Small-Molecule Inhibitor of Aurora A Kinase Using Novel in Vivo Pharmacodynamic Assays","volume":"17","author":"Manfredi","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6928","DOI":"10.7150\/thno.43811","article-title":"Aurora-A\/SOX8\/FOXK1 Signaling Axis Promotes Chemoresistance via Suppression of Cell Senescence and Induction of Glucose Metabolism in Ovarian Cancer Organoids and Cells","volume":"10","author":"Sun","year":"2020","journal-title":"Theranostics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1158\/1541-7786.MCR-13-0044","article-title":"AURKA Governs Self-Renewal Capacity in Glioma-Initiating Cells via Stabilization\/Activation of \u03b2-Catenin\/Wnt Signaling","volume":"11","author":"Xia","year":"2013","journal-title":"Mol. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/onc.2012.628","article-title":"The Mitotic Kinase Aurora-A Promotes Distant Metastases by Inducing Epithelial-to-Mesenchymal Transition in ER + Breast Cancer Cells","volume":"33","author":"Liu","year":"2014","journal-title":"Oncogene"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1016\/j.apsb.2023.03.013","article-title":"Emerging Roles of Aurora-A Kinase in Cancer Therapy Resistance","volume":"13","author":"Zheng","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13008-024-00125-x","article-title":"Mitotic Kinases Are Emerging Therapeutic Targets against Metastatic Breast Cancer","volume":"19","author":"Saavedra","year":"2024","journal-title":"Cell Div."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13000-021-01158-4","article-title":"Aurora-A Kinase Is Differentially Expressed in the Nucleus and Cytoplasm in Normal M\u00fcllerian Epithelium and Benign, Borderline and Malignant Serous Ovarian Neoplasms","volume":"16","author":"Alkhateeb","year":"2021","journal-title":"Diagn. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1038\/ncomms3126","article-title":"Evaluating Cell Lines as Tumour Models by Comparison of Genomic Profiles","volume":"4","author":"Domcke","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1177\/2472555220915827","article-title":"Comparison of Cell and Organoid-Level Analysis of Patient-Derived 3D Organoids to Evaluate Tumor Cell Growth Dynamics and Drug Response","volume":"25","author":"Kim","year":"2020","journal-title":"SLAS Discov."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Cody, N.A., Zietarska, M., Filali-Mouhim, A., Provencher, D.M., Mes-Masson, A.-M., and Tonin, P.N. (2008). Influence of Monolayer, Spheroid, and Tumor Growth Conditions on Chromosome 3 Gene Expression in Tumorigenic Epithelial Ovarian Cancer Cell Lines. BMC Med. Genom., 1.","DOI":"10.1186\/1755-8794-1-34"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI Gene Expression and Hybridization Array Data Repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:30:50Z","timestamp":1759919450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cells14020133"],"URL":"https:\/\/doi.org\/10.3390\/cells14020133","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]}}}