{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:44:00Z","timestamp":1789839840947,"version":"4.0.1"},"reference-count":200,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR dysregulation in endometriosis and EAOCs, investigating cancer driver gene mutations and their potential interaction with the mTOR pathway. Additionally, we explore the complex pathogenesis of transformation, considering environmental, hormonal, and epigenetic factors. We then discuss postmenopausal endometriosis pathogenesis and propensity for malignant transformation. Finally, we summarize the current advancements in mTOR-targeted therapeutics for endometriosis and EAOCs.<\/jats:p>","DOI":"10.3390\/cancers16112160","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T06:40:26Z","timestamp":1717656026000},"page":"2160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The \u201cRoad\u201d to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Radwa","family":"Hablase","sequence":"first","affiliation":[{"name":"College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB83PH, UK"},{"name":"Academic Department of Gynaecological Oncology, Royal Surrey NHS Foundation Trust Hospital, Guildford GU2 7XX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-3439","authenticated-orcid":false,"given":"Ioannis","family":"Kyrou","sequence":"additional","affiliation":[{"name":"Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK"},{"name":"Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK"},{"name":"Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK"},{"name":"Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry CV1 5FB, UK"},{"name":"Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK"},{"name":"College of Health, Psychology and Social Care, University of Derby, Derby DE22 1GB, UK"},{"name":"Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, 11855 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harpal","family":"Randeva","sequence":"additional","affiliation":[{"name":"Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK"},{"name":"Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK"},{"name":"Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK"},{"name":"Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry CV1 5FB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouil","family":"Karteris","sequence":"additional","affiliation":[{"name":"College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB83PH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-4835","authenticated-orcid":false,"given":"Jayanta","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB83PH, UK"},{"name":"Academic Department of Gynaecological Oncology, Royal Surrey NHS Foundation Trust Hospital, Guildford GU2 7XX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/ijgo.13878","article-title":"Cancer of the ovary, fallopian tube, and peritoneum: 2021 update","volume":"155","author":"Berek","year":"2021","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_2","first-page":"686","article-title":"Ovarian tumors. A review","volume":"87","author":"Scully","year":"1977","journal-title":"Am. J. Pathol."},{"key":"ref_3","unstructured":"(1971). Classification and staging of malignant tumours in the female pelvis. Acta Obstet. Gynecol. Scand., 50, 1\u20137."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"De Leo, A., Santini, D., Ceccarelli, C., Santandrea, G., Palicelli, A., Acquaviva, G., Chiarucci, F., Rosini, F., Ravegnini, G., and Pession, A. (2021). What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors. Diagnostics, 11.","DOI":"10.3390\/diagnostics11040697"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"K\u00f6bel, M., and Kang, E.Y. (2022). The Evolution of Ovarian Carcinoma Subclassification. Cancers, 14.","DOI":"10.3390\/cancers14020416"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/his.13970","article-title":"Endometriosis-related pathology: A discussion of selected uncommon benign, premalignant and malignant lesions","volume":"76","author":"McCluggage","year":"2020","journal-title":"Histopathology"},{"key":"ref_7","first-page":"869","article-title":"Tubal origin of ovarian endometriosis and clear cell and endometrioid carcinoma","volume":"5","author":"Wang","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bartiromo, L., Schimberni, M., Villanacci, R., Mangili, G., Ferrari, S., Ottolina, J., Salmeri, N., Dolci, C., Tandoi, I., and Candiani, M. (2022). A Systematic Review of Atypical Endometriosis-Associated Biomarkers. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084425"},{"key":"ref_9","first-page":"91","article-title":"Endometriosis\u2014Clinical approach based on histological findings","volume":"54","author":"Cristescu","year":"2013","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106","DOI":"10.2174\/1573404813666170306163448","article-title":"Molecular and Cellular Pathogenesis of Endometriosis","volume":"14","author":"Klemmt","year":"2017","journal-title":"Curr. Women Health Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mce.2018.12.011","article-title":"Dual inhibition of ERK1\/2 and AKT pathways is required to suppress the growth and survival of endometriotic cells and lesions","volume":"484","author":"Arosh","year":"2019","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1007\/s00261-019-02309-4","article-title":"Endometriosis in the postmenopausal female: Clinical presentation, imaging features, and management","volume":"45","author":"Cope","year":"2020","journal-title":"Abdom. Radiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.rbms.2021.07.003","article-title":"The missed disease? Endometriosis as an example of \u2018undone science\u2019","volume":"14","author":"Hudson","year":"2022","journal-title":"Reprod. Biomed. Soc. Online"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1111\/aogs.14583","article-title":"Endometriosis and menopause\u2014Management strategies based on clinical scenarios","volume":"102","author":"Jakson","year":"2023","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1136\/jcp.2007.050971","article-title":"A detailed morphologic and immunohistochemical comparison of pre- and postmenopausal endometriosis","volume":"61","author":"Cumiskey","year":"2008","journal-title":"J. Clin. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.18632\/oncotarget.23364","article-title":"Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma","volume":"9","author":"Chang","year":"2018","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Murakami, K., Kotani, Y., Nakai, H., and Matsumura, N. (2020). Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy. Cancers, 12.","DOI":"10.3390\/cancers12061676"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yachida, N., Yoshihara, K., Yamaguchi, M., Suda, K., Tamura, R., and Enomoto, T. (2021). How Does Endometriosis Lead to Ovarian Cancer? The Molecular Mechanism of Endometriosis-Associated Ovarian Cancer Development. Cancers, 13.","DOI":"10.3390\/cancers13061439"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"286","DOI":"10.23736\/S0026-4784.17.04042-4","article-title":"Ovarian cancer in endometriosis: An update on the clinical and molecular aspects","volume":"69","author":"Ruderman","year":"2017","journal-title":"Minerva Obstet. Gynecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/PGP.0b013e31821f4b85","article-title":"Endometriosis and ovarian cancer: A review of clinical, pathologic, and molecular aspects","volume":"30","author":"Wei","year":"2011","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1007\/s12325-020-01363-5","article-title":"Malignant Transformation and Associated Biomarkers of Ovarian Endometriosis: A Narrative Review","volume":"37","author":"Mikhaleva","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13048-021-00865-2","article-title":"Association between atypical endometriosis and ovarian malignancies in the real world","volume":"14","author":"So","year":"2021","journal-title":"J. Ovarian Res."},{"key":"ref_23","first-page":"47","article-title":"Differential expression of mTOR components in endometriosis and ovarian cancer: Effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry","volume":"43","author":"Kumar","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1038\/emboj.2009.281","article-title":"Emerging common themes in regulation of PIKKs and PI3Ks","volume":"28","author":"Halazonetis","year":"2009","journal-title":"EMBO J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ceb.2017.02.012","article-title":"mTORC1 signaling and the metabolic control of cell growth","volume":"45","author":"Manning","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.transproceed.2008.10.009","article-title":"mTOR-what does it do?","volume":"40","author":"Hall","year":"2008","journal-title":"Transpl. Proc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1101\/gad.1212704","article-title":"Upstream and downstream of mTOR","volume":"18","author":"Hay","year":"2004","journal-title":"Genes. Dev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Paquette, M., El-Houjeiri, L., and Pause, A. (2018). mTOR Pathways in Cancer and Autophagy. Cancers, 10.","DOI":"10.3390\/cancers10010018"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2967\/jnumed.111.089623","article-title":"mTOR signaling, function, novel inhibitors, and therapeutic targets","volume":"52","author":"Watanabe","year":"2011","journal-title":"J. Nucl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.molcel.2010.05.017","article-title":"Structure of the human mTOR complex I and its implications for rapamycin inhibition","volume":"38","author":"Yip","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e99548","DOI":"10.15252\/embj.201899548","article-title":"RagC phosphorylation autoregulates mTOR complex 1","volume":"38","author":"Yang","year":"2019","journal-title":"EMBO J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14","DOI":"10.12688\/f1000research.16109.1","article-title":"Cryo-EM insight into the structure of MTOR complex 1 and its interactions with Rheb and substrates","volume":"8","author":"Chao","year":"2019","journal-title":"F1000Research"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.tibs.2003.09.003","article-title":"Rheb fills a GAP between TSC and TOR","volume":"28","author":"Manning","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_34","first-page":"E1453","article-title":"Role of PRAS40 in Akt and mTOR signaling in health and disease","volume":"302","author":"Wiza","year":"2012","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kakumoto, K., Ikeda, J., Okada, M., Morii, E., and Oneyama, C. (2015). mLST8 Promotes mTOR-Mediated Tumor Progression. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119015"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e33101","DOI":"10.7554\/eLife.33101","article-title":"Architecture of the human mTORC2 core complex","volume":"7","author":"Stuttfeld","year":"2018","journal-title":"eLlife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"eabc1251","DOI":"10.1126\/sciadv.abc1251","article-title":"The 3.2-\u00c5 resolution structure of human mTORC2","volume":"6","author":"Scaiola","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.devcel.2006.10.007","article-title":"Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1","volume":"11","author":"Guertin","year":"2006","journal-title":"Dev. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e19594","DOI":"10.7554\/eLife.19594","article-title":"Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit","volume":"6","author":"Tatebe","year":"2017","journal-title":"Elife"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e70871","DOI":"10.7554\/eLife.70871","article-title":"Regulation of human mTOR complexes by DEPTOR","volume":"10","author":"Berneiser","year":"2021","journal-title":"Elife"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e68799","DOI":"10.7554\/eLife.68799","article-title":"Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace","volume":"10","author":"Heimhalt","year":"2021","journal-title":"Elife"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.molcel.2007.03.003","article-title":"PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase","volume":"25","author":"Sancak","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12970-016-0118-y","article-title":"Regulation of mTORC1 by growth factors, energy status, amino acids and mechanical stimuli at a glance","volume":"13","author":"Bond","year":"2016","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.molcel.2012.06.009","article-title":"TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1","volume":"47","author":"Dibble","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4104","DOI":"10.1128\/MCB.00289-08","article-title":"The TSC1-TSC2 Complex Is Required for Proper Activation of mTOR Complex 2","volume":"28","author":"Huang","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1083\/jcb.201610060","article-title":"Localization of mTORC2 activity inside cells","volume":"216","author":"Ebner","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12964-022-00859-7","article-title":"mTORC2: A multifaceted regulator of autophagy","volume":"21","author":"Sun","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Rigoulet, M., Bouchez, C., Paumard, P., Ransac, S., Cuvellier, S., Duvezin-Caubet, S., Mazat, J., and Devin, A. (2020). Cell energy metabolism: An update. Biochim. Biophys. Acta Bioenerg., 1861.","DOI":"10.1016\/j.bbabio.2020.148276"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tondo-Steele, K., and McLean, K. (2022). The \u201cSweet Spot\u201d of Targeting Tumor Metabolism in Ovarian Cancers. Cancers, 14.","DOI":"10.3390\/cancers14194696"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"104511","DOI":"10.1016\/j.phrs.2019.104511","article-title":"Targeting glucose metabolism to suppress cancer progression: Prospective of anti-glycolytic cancer therapy","volume":"150","author":"Mahmoud","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.molcel.2010.06.022","article-title":"Activation of a metabolic gene regulatory network downstream of mTOR complex 1","volume":"39","author":"Yecies","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1042\/BST0390495","article-title":"Regulation of the SREBP transcription factors by mTORC1","volume":"39","author":"Lewis","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1080\/15384101.2016.1151581","article-title":"4E-BP1, a multifactor regulated multifunctional protein","volume":"15","author":"Qin","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1023\/B:APPT.0000045781.46314.e2","article-title":"Bcl-2 and CCND1\/CDK4 expression levels predict the cellular effects of mTOR inhibitors in human ovarian carcinoma","volume":"9","author":"Aguirre","year":"2004","journal-title":"Apoptosis"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Yi, Y.W., You, K.S., Park, J.S., Lee, S.G., and Seong, Y.S. (2022). Ribosomal protein S6: A potential therapeutic target against cancer?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010048"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Taucher, E., Mykoliuk, I., Fediuk, M., and Smolle-Juettner, F.-M. (2022). Autophagy, Oxidative Stress and Cancer Development. Cancers, 14.","DOI":"10.3390\/cancers14071637"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Errafiy, R., Aguado, C., Ghislat, G., Esteve, J.M., Gil, A., Loutfi, M., and Knecht, E. (2013). PTEN increases autophagy and inhibits the ubiquitin-proteasome pathway in glioma cells independently of its lipid phosphatase activity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083318"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1096\/fj.201700477R","article-title":"Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer","volume":"32","author":"Yang","year":"2018","journal-title":"FASEB J."},{"key":"ref_59","first-page":"3837","article-title":"Autophagy-induced tumor dormancy in ovarian cancer","volume":"118","author":"Amaravadi","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1757-2215-5-22","article-title":"Involvement of autophagy in ovarian cancer: A working hypothesis","volume":"5","author":"Peracchio","year":"2012","journal-title":"J. Ovarian Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0002-9378(15)30003-X","article-title":"iPeritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity","volume":"14","author":"Sampson","year":"1927","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.fertnstert.2012.06.029","article-title":"Pathogenesis and pathophysiology of endometriosis","volume":"98","author":"Burney","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3109\/00016345509158287","article-title":"The pathogenesis of endometriosis; an experimental study","volume":"34","author":"Levander","year":"1955","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Maruyama, T. (2022). A Revised Stem Cell Theory for the Pathogenesis of Endometriosis. J. Pers. Med., 12.","DOI":"10.3390\/jpm12020216"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ejogrb.2020.08.019","article-title":"Relationship between adenomyosis and endometriosis; Different phenotypes of a single disease?","volume":"253","author":"Maruyama","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"hoab025","DOI":"10.1093\/hropen\/hoab025","article-title":"Endometriosis classification, staging and reporting systems: A review on the road to a universally accepted endometriosis classification","volume":"2021","author":"Vermeulen","year":"2021","journal-title":"Hum. Reprod. Open"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"(1997). Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil. Steril., 67, 817\u2013821.","DOI":"10.1016\/S0015-0282(97)81391-X"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"hoac009","DOI":"10.1093\/hropen\/hoac009","article-title":"ESHRE guideline: Endometriosis","volume":"2022","author":"Becker","year":"2022","journal-title":"Hum. Reprod. Open"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"F1000","DOI":"10.12688\/f1000research.14817.1","article-title":"Endometriosis: Advances and controversies in classification, pathogenesis, diagnosis, and treatment","volume":"8","author":"Rolla","year":"2019","journal-title":"F1000Research"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zhang, P., and Wang, G. (2023). Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24086992"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1002\/mrd.22493","article-title":"Non-hormonal targets underlying endometriosis: A focus on molecular mechanisms","volume":"82","author":"Che","year":"2015","journal-title":"Mol. Reprod. Dev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"692","DOI":"10.3389\/fendo.2019.00692","article-title":"Role of mTOR Signaling in Female Reproduction","volume":"10","author":"Guo","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/molehr\/gat091","article-title":"Differential induction of autophagy by mTOR is associated with abnormal apoptosis in ovarian endometriotic cysts","volume":"20","author":"Choi","year":"2014","journal-title":"Mol. Hum. Reprod."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Chantalat, E., Valera, M.-C., Vaysse, C., Noirrit, E., Rusidze, M., Weyl, A., Vergriete, K., Buscail, E., Lluel, P., and Fontaine, C. (2020). Estrogen Receptors and Endometriosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082815"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"120805","DOI":"10.1016\/j.lfs.2022.120805","article-title":"Role of AMPK\/mTOR, mitochondria, and ROS in the pathogenesis of endometriosis","volume":"306","author":"Assaf","year":"2022","journal-title":"Life Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.rbmo.2012.01.022","article-title":"The eutopic endometrium in endometriosis: Are the changes of clinical significance?","volume":"24","author":"Brosens","year":"2012","journal-title":"Reprod. Biomed. Online"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.rbmo.2009.10.001","article-title":"Differential regulation of Akt phosphorylation in endometriosis","volume":"19","author":"Cinar","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41598-019-57207-y","article-title":"Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I\u2013II and III\u2013IV endometriosis independently of hormonal milieu","volume":"10","author":"Meola","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1210\/en.2013-1951","article-title":"Activated AKT pathway promotes establishment of endometriosis","volume":"155","author":"Kim","year":"2014","journal-title":"Endocrinology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1530\/REP-16-0322","article-title":"Aberrant PTEN expression in response to progesterone reduces endometriotic stromal cell apoptosis","volume":"153","author":"Choi","year":"2017","journal-title":"Reproduction"},{"key":"ref_81","first-page":"4707","article-title":"Autophagy in endometriosis","volume":"9","author":"Yang","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Choi, J., Jo, M., Lee, E., Oh, Y.K., and Choi, D. (2012). The role of autophagy in human endometrium1. Biol. Reprod., 86.","DOI":"10.1095\/biolreprod.111.096206"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/bs.apcsb.2019.01.001","article-title":"Estrogen receptor signaling mechanisms","volume":"116","author":"Fuentes","year":"2019","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/320134a0","article-title":"Human oestrogen receptor cDNA: Sequence, expression and homology to v-erb-A","volume":"320","author":"Green","year":"1986","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2015.10.034","article-title":"Estrogen Receptor \u03b2 Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis","volume":"163","author":"Han","year":"2015","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Samartzis, N., Samartzis, E.P., Noske, A., Fedier, A., Dedes, K.J., Caduff, R., Fink, D., and Imesch, P. (2012). Expression of the G protein-coupled estrogen receptor (GPER) in endometriosis: A tissue microarray study. Reprod. Biol. Endocrinol., 10.","DOI":"10.1186\/1477-7827-10-30"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jri.2012.10.013","article-title":"Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis: Potential implications for macrophages and follicle maturation","volume":"97","author":"Heublein","year":"2013","journal-title":"J. Reprod. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.fertnstert.2015.01.026","article-title":"G protein-coupled estrogen receptor 1 agonist G-1 induces cell cycle arrest in the mitotic phase, leading to apoptosis in endometriosis","volume":"103","author":"Mori","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/jog.13372","article-title":"New knowledge and insights about the malignant transformation of endometriosis","volume":"43","author":"Taniguchi","year":"2017","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1006\/gyno.1996.0032","article-title":"Histologic transformation of benign endometriosis to early epithelial ovarian cancer","volume":"60","author":"Eichhorn","year":"1996","journal-title":"Gynecol. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/aogs.12255","article-title":"The relation between endometriosis and ovarian cancer\u2014A review","volume":"93","author":"Heidemann","year":"2014","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fsurg.2014.00014","article-title":"Endometriosis and ovarian cancer risk: A systematic review of epidemiological studies","volume":"1","author":"Zafrakas","year":"2014","journal-title":"Front. Surg."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"347","DOI":"10.23736\/S2724-606X.21.04757-2","article-title":"The relation between endometrioma and ovarian cancer","volume":"73","author":"Sorbi","year":"2021","journal-title":"Minerva Obstet. Gynecol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1470-2045(11)70404-1","article-title":"Association between endometriosis and risk of histological subtypes of ovarian cancer: A pooled analysis of case\u2013control studies","volume":"13","author":"Pearce","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_95","first-page":"283","article-title":"Malignant changes in endometriosis","volume":"2","author":"Scott","year":"1953","journal-title":"Obstet. Gynecol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1006\/gyno.2000.5765","article-title":"Ovarian endometriosis associated with ovarian carcinoma: A clinicopathological and immunohistochemical study","volume":"77","author":"Ogawa","year":"2000","journal-title":"Gynecol. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ygyno.2005.11.033","article-title":"Association between endometriosis and cancer: A comprehensive review and a critical analysis of clinical and epidemiological evidence","volume":"101","author":"Somigliana","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Bergamini, A., Mangili, G., Ambrosi, A., Taccagni, G., Rabaiotti, E., Bocciolone, L., Candotti, G., Cioffi, R., Pella, F., and Sabetta, G. (2023). Endometriosis-Related Ovarian Cancers: Evidence for a Dichotomy in the Histogenesis of the Two Associated Histotypes. Diagnostics, 13.","DOI":"10.3390\/diagnostics13081425"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1046\/j.1365-2559.1997.d01-592.x","article-title":"Ovarian atypical endometriosis: Its close association with malignant epithelial tumours","volume":"30","author":"Fukunaga","year":"1997","journal-title":"Histopathology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00004347-199601000-00001","article-title":"Prognostic importance of hyperplasia and atypia in endometriosis","volume":"15","author":"Seidman","year":"1996","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000496178","article-title":"Long-Term Follow-Up after Surgical Management for Atypical Endometriosis: A Series of Nine Cases","volume":"12","author":"Tanase","year":"2019","journal-title":"Case Rep. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Centini, G., Schettini, G., Pieri, E., Giorgi, M., Lazzeri, L., Martire, F.G., Mancini, V., Raimondo, D., Seracchioli, R., and Habib, N. (2024). Endometriosis-Related Ovarian Cancer: Where Are We Now? A Narrative Review towards a Pragmatic Approach. J. Clin. Med., 13.","DOI":"10.3390\/jcm13071933"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1309\/AJCPZ5T2POOFMQVN","article-title":"Distinct \u03b2-catenin and PIK3CA Mutation profiles in endometriosis-associated ovarian endometrioid and clear cell carcinomas","volume":"144","author":"Matsumoto","year":"2015","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/modpathol.2011.189","article-title":"Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations","volume":"25","author":"Yamamoto","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1097\/IGC.0b013e31826b5dcc","article-title":"Loss of ARID1A Expression Is an Early Molecular Event in Tumor Progression From Ovarian Endometriotic Cyst to Clear Cell and Endometrioid Carcinoma","volume":"22","author":"Ayhan","year":"2012","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7678","DOI":"10.1158\/0008-5472.CAN-04-2933","article-title":"Mutation of the PIK3CA Gene in Ovarian and Breast Cancer","volume":"64","author":"Campbell","year":"2004","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00428-011-1169-8","article-title":"PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma","volume":"460","author":"Yamamoto","year":"2012","journal-title":"Virchows Arch."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/path.2940","article-title":"PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma","volume":"225","author":"Yamamoto","year":"2011","journal-title":"J. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/path.4516","article-title":"Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden","volume":"236","author":"Anglesio","year":"2015","journal-title":"J. Pathol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1056\/NEJMoa1614814","article-title":"Cancer-Associated Mutations in Endometriosis without Cancer","volume":"376","author":"Anglesio","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1038\/s41379-021-00861-3","article-title":"Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma","volume":"34","author":"Murakami","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1080\/09513590.2019.1680627","article-title":"PI3K\/AKT pathway is altered in the endometriosis patient\u2019s endometrium and presents differences according to severity stage","volume":"36","author":"Madanes","year":"2020","journal-title":"Gynecol. Endocrinol."},{"key":"ref_113","first-page":"7052","article-title":"Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: Possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary","volume":"60","author":"Sato","year":"2000","journal-title":"Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/humrep\/det387","article-title":"Mutations in the PTEN tumor gene and risk of endometriosis: A case\u2013control study","volume":"29","author":"Govatati","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2014.07.018","article-title":"Vulnerabilities of Mutant SWI\/SNF Complexes in Cancer","volume":"26","author":"Helming","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1008433","article-title":"ARID1A mutations in endometriosis-associated ovarian carcinomas","volume":"363","author":"Wiegand","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/modpathol.2011.217","article-title":"Loss of ARID1A\/BAF250a-expression in endometriosis: A biomarker for risk of carcinogenic transformation?","volume":"25","author":"Samartzis","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.21037\/atm-20-3022a","article-title":"Endometriosis-associated ovarian carcinomas: Insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review","volume":"8","author":"Samartzis","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"14260","DOI":"10.1038\/s41598-020-71273-7","article-title":"ARID1A protein expression is retained in ovarian endometriosis with ARID1A loss-of-function mutations: Implication for the two-hit hypothesis","volume":"10","author":"Yachida","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1073\/pnas.68.4.820","article-title":"Mutation and Cancer: Statistical Study of Retinoblastoma","volume":"68","author":"Knudson","year":"1971","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1136\/ijgc-2020-001656","article-title":"Clear cell carcinoma of the ovary: A clinical and molecular perspective","volume":"31","author":"Iida","year":"2021","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1038\/modpathol.2013.96","article-title":"Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer","volume":"26","author":"Bosse","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ijgo.2015.02.021","article-title":"The ARID1A pathway in ovarian clear cell and endometrioid carcinoma, contiguous endometriosis, and benign endometriosis","volume":"130","author":"Chene","year":"2015","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"dju146","DOI":"10.1093\/jnci\/dju146","article-title":"Roles of deletion of arid1a, a tumor suppressor, in mouse ovarian tumorigenesis","volume":"106","author":"Guan","year":"2014","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nm1173","article-title":"Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer","volume":"11","author":"Dinulescu","year":"2005","journal-title":"Nat. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"6118","DOI":"10.1038\/ncomms7118","article-title":"Coexistent ARID1A\u2013PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling","volume":"6","author":"Chandler","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nm.3799","article-title":"Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers","volume":"21","author":"Bitler","year":"2015","journal-title":"Nat. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"5295","DOI":"10.18632\/oncotarget.2092","article-title":"Loss of ARID1A expression sensitizes cancer cells to PI3K- and AKT-inhibition","volume":"5","author":"Samartzis","year":"2014","journal-title":"Oncotarget"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.celrep.2018.07.037","article-title":"Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium","volume":"24","author":"Suda","year":"2018","journal-title":"Cell Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"832228","DOI":"10.3389\/fonc.2022.832228","article-title":"Deep Infiltrating Endometriosis Malignant Invasion of Cervical Wall and Rectal Wall with Lynch Syndrome: A Rare Case Report and Review of Literature","volume":"12","author":"Li","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1158\/1078-0432.CCR-07-1614","article-title":"Contents of Endometriotic Cysts, Especially the High Concentration of Free Iron, Are a Possible Cause of Carcinogenesis in the Cysts through the Iron-Induced Persistent Oxidative Stress","volume":"14","author":"Yamaguchi","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1177\/1933719117704909","article-title":"Role of Oxidative Stress in Epigenetic Modification in Endometriosis","volume":"24","author":"Ito","year":"2017","journal-title":"Reprod. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0002-9378(97)70550-7","article-title":"Cancer risk after a hospital discharge diagnosis of endometriosis","volume":"176","author":"Brinton","year":"1997","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Terzic, M., Aimagambetova, G., Kunz, J., Bapayeva, G., Aitbayeva, B., Terzic, S., and Lagan\u00e0, A.S. (2021). Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179274"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1101\/gad.14.16.1983","article-title":"HIF-1 and human disease: One highly involved factor","volume":"14","author":"Semenza","year":"2000","journal-title":"Genes. Dev."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.tjog.2012.01.010","article-title":"Estrogen receptor expression affected by hypoxia inducible factor-1\u03b1 in stromal cells from patients with endometriosis","volume":"51","author":"Wu","year":"2012","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"534","DOI":"10.2353\/ajpath.2008.061244","article-title":"2-methoxyestradiol inhibits hypoxia-inducible factor-1{alpha} and suppresses growth of lesions in a mouse model of endometriosis","volume":"172","author":"Becker","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/jog.13900","article-title":"Hypoxia: The force of endometriosis","volume":"45","author":"Wu","year":"2019","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.biochi.2016.01.006","article-title":"Hypoxia-inducible factor-1alpha: A promising therapeutic target in endometriosis","volume":"123","author":"Zhan","year":"2016","journal-title":"Biochimie"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.apsb.2015.05.007","article-title":"HIF-1\u03b1 pathway: Role, regulation and intervention for cancer therapy","volume":"5","author":"Masoud","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/jog.15083","article-title":"LncRNA HCG11 represses ovarian cancer cell growth via AKT signaling pathway","volume":"48","author":"Chen","year":"2022","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2151354","DOI":"10.1080\/01443615.2022.2151354","article-title":"Effects of MFG-E8 expression on the biological characteristics of ovarian cancer cells via the AKT\/mTOR\/S6K signalling pathway","volume":"43","author":"Li","year":"2023","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s12967-022-03422-7","article-title":"miR-18a-5p derived from mesenchymal stem cells-extracellular vesicles inhibits ovarian cancer cell proliferation, migration, invasion, and chemotherapy resistance","volume":"20","author":"Wang","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.bbrc.2022.10.091","article-title":"Silencing of lncRNA SNHG17 inhibits the tumorigenesis of epithelial ovarian cancer through regulation of miR-485-5p\/AKT1 axis","volume":"637","author":"Wang","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrfmmm.2018.03.001","article-title":"The presence of KRAS, PPP2R1A and ARID1A mutations in 101 Chinese samples with ovarian endometriosis","volume":"809","author":"Zou","year":"2018","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_146","first-page":"642","article-title":"Loss of ARID1A\/BAF250a expression in ovarian endometriosis and clear cell carcinoma","volume":"5","author":"Xiao","year":"2012","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/molehr\/gaw009","article-title":"(Partial) Loss of BAF250a (ARID1A) in rectovaginal deep-infiltrating endometriosis, endometriomas and involved pelvic sentinel lymph nodes","volume":"22","author":"Borrelli","year":"2016","journal-title":"Mol. Hum. Reprod."},{"key":"ref_148","first-page":"287","article-title":"Endometriosis and the estrogen threshold theory. Relation to surgical and medical treatment","volume":"43","author":"Barbieri","year":"1998","journal-title":"J. Reprod. Med."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Giannella, L., Marconi, C., Di Giuseppe, J., Carpini, G.D., Fichera, M., Grelloni, C., Giuliani, L., Montanari, M., Insinga, S., and Ciavattini, A. (2021). Malignant Transformation of Postmenopausal Endometriosis: A Systematic Review of the Literature. Cancers, 13.","DOI":"10.3390\/cancers13164026"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Lee, H.J., Lee, B., Choi, H., Kim, T., Kim, Y., and Kim, Y.B. (2023). Impact of Hormone Replacement Therapy on Risk of Ovarian Cancer in Postmenopausal Women with De Novo Endometriosis or a History of Endometriosis. Cancers, 15.","DOI":"10.3390\/cancers15061708"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1749-6632.2002.tb02767.x","article-title":"Estrogen Production and Metabolism in Endometriosis","volume":"955","author":"Bulun","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_152","first-page":"600","article-title":"Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells","volume":"82","author":"Noble","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/nyas.12411","article-title":"Aromatase and endometriosis: Estrogens play a role","volume":"1317","author":"Ferrero","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3934","DOI":"10.1210\/en.2003-0289","article-title":"Transactivation of steroidogenic acute regulatory protein in human endometriotic stromalcells is mediated by the prostaglandin EP2 receptor","volume":"144","author":"Sun","year":"2003","journal-title":"Endocrinology"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/rmb2.12285","article-title":"Local estrogen formation and its regulation in endometriosis","volume":"18","author":"Mori","year":"2019","journal-title":"Reprod. Med. Biol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s10397-019-1056-x","article-title":"Symptomatic endometriosis developing several years after menopause in the absence of increased circulating estrogen concentrations: A systematic review and seven case reports","volume":"16","author":"Ribeiro","year":"2019","journal-title":"Gynecol. Surg."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Watrowski, R., Schuster, E., Hofstetter, G., Fischer, M.B., Mahner, S., Van Gorp, T., Polterauer, S., Zeillinger, R., and Obermayr, E. (2024). Association of Four Interleukin-8 Polymorphisms (\u2212251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes. Biomedicines, 12.","DOI":"10.3390\/biomedicines12020321"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Secosan, C., Balulescu, L., Brasoveanu, S., Balint, O., Pirtea, P., Dorin, G., and Pirtea, L. (2020). Endometriosis in Menopause\u2014Renewed Attention on a Controversial Disease. Diagnostics, 10.","DOI":"10.3390\/diagnostics10030134"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1080\/13697137.2018.1450855","article-title":"Postmenopausal endometriosis: Drawing a clearer clinical picture","volume":"21","author":"Tan","year":"2018","journal-title":"Climacteric"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1080\/13697137.2017.1284781","article-title":"Endometriosis after menopause: Physiopathology and management of an uncommon condition","volume":"20","author":"Streuli","year":"2017","journal-title":"Climacteric"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Benagiano, G., and Guo, S. (2022). Age-dependent phenotypes of ovarian endometriomas. Reprod. Med. Biol., 21.","DOI":"10.1002\/rmb2.12438"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ejogrb.2007.06.017","article-title":"Ovarian endometrioma\u2014Risks factors of ovarian cancer development","volume":"138","author":"Kobayashi","year":"2008","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1055\/s-0035-1558239","article-title":"Endometriosis-associated Malignancy","volume":"76","author":"Krawczyk","year":"2016","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1055\/s-2003-42277","article-title":"[Endometriosis and malignoma]","volume":"125","author":"Ulrich","year":"2003","journal-title":"Zentralbl. Gynakol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1136\/ijgc-00009577-200511000-00041","article-title":"Parametrial and rectovaginal adenocarcinoma arising from endometriosis","volume":"15","author":"Ulrich","year":"2005","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e922973","DOI":"10.12659\/AJCR.922973","article-title":"Endometrioid Carcinoma Arising from an Endometriosis-Associated Abdominal Wall Scar","volume":"21","author":"Paulino","year":"2020","journal-title":"Am. J. Case Rep."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Driva, T.S., Schatz, C., and Haybaeck, J. (2023). Endometriosis-Associated Ovarian Carcinomas: How PI3K\/AKT\/mTOR Pathway Affects Their Pathogenesis. Biomolecules, 13.","DOI":"10.3390\/biom13081253"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1136\/ijgc-00009577-200607000-00008","article-title":"Activation of mammalian target of rapamycin in postmenopausal ovarian endometriosis","volume":"16","author":"Yagyu","year":"2006","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/aogs.13010","article-title":"Risk factors of epithelial ovarian carcinomas among women with endometriosis: A systematic review","volume":"96","author":"Thomsen","year":"2016","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1002\/med.21802","article-title":"Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review","volume":"41","author":"Hung","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ygyno.2014.02.017","article-title":"mTOR inhibitors and their clinical application in cervical, endometrial and ovarian cancers: A critical review","volume":"133","author":"Husseinzadeh","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_172","first-page":"721","article-title":"Rapamycin (AY-22,989), a new antifungal antibiotic","volume":"28","author":"Kudelski","year":"1975","journal-title":"I. Taxonomy of the producing streptomycete and isolation of the active principle. J. Antibiot."},{"key":"ref_173","first-page":"1225","article-title":"New antirejection drugs anticipated","volume":"264","author":"Randall","year":"1990","journal-title":"JAMA"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/0277-5379(83)90012-3","article-title":"Human brain tumor xenografts in nude mice as a chemotherapy model","volume":"19","author":"Houchens","year":"1983","journal-title":"Eur. J. Cancer Clin. Oncol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1074\/jbc.270.2.815","article-title":"Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells","volume":"270","author":"Sabers","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0092-8674(93)90144-F","article-title":"Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression","volume":"73","author":"Kunz","year":"1993","journal-title":"Cell"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Kajiwara, M., and Masuda, S. (2016). Role of mTOR Inhibitors in Kidney Disease. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060975"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.4161\/cbt.22859","article-title":"Rapalogs in cancer prevention: Anti-aging or anticancer?","volume":"13","author":"Blagosklonny","year":"2012","journal-title":"Cancer Biol. Ther."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"3693625","DOI":"10.1155\/2018\/3693625","article-title":"Therapeutic Use of mTOR Inhibitors in Renal Diseases: Advances, Drawbacks, and Challenges","volume":"2018","author":"Viana","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Vargas-Toscano, A., Nickel, A.-C., Li, G., Kamp, M.A., Muhammad, S., Leprivier, G., Fritsche, E., Barker, R.A., Sabel, M., and Steiger, H.-J. (2020). Rapalink-1 Targets Glioblastoma Stem Cells and Acts Synergistically with Tumor Treating Fields to Reduce Resistance against Temozolomide. Cancers, 12.","DOI":"10.3390\/cancers12123859"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41420-018-0060-7","article-title":"NVP-BEZ235, a dual PI3K-mTOR inhibitor, suppresses the growth of FaDu hypopharyngeal squamous cell carcinoma and has a synergistic effect with Cisplatin","volume":"4","author":"Hsu","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Skorda, A., Bay, M.L., Hautaniemi, S., Lahtinen, A., and Kallunki, T. (2022). Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises. Cancers, 14.","DOI":"10.3390\/cancers14246257"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1016\/j.fertnstert.2015.07.493","article-title":"Dienogest enhances autophagy induction in endometriotic cells by impairing activation of AKT, ERK1\/2, and mTOR","volume":"104","author":"Choi","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3892\/etm.2016.3280","article-title":"Effect of rapamycin on endometriosis in mice","volume":"12","author":"Ren","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1055\/s-0042-115566","article-title":"Everolimus as an mTOR Inhibitor Suppresses Endometriotic Implants: An Experimental Rat Study","volume":"77","author":"Kacan","year":"2017","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1111\/bph.14170","article-title":"In vitro and in vivo effects of MK2206 and chloroquine combination therapy on endometriosis: Autophagy may be required for regrowth of endometriosis","volume":"175","author":"Matsuzaki","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1055\/s-0043-124518","article-title":"mTor Inhibitors for the Treatment of Endometriosis","volume":"78","author":"Barra","year":"2018","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/path.6006","article-title":"The proteome of clear cell ovarian carcinoma","volume":"258","author":"Ji","year":"2022","journal-title":"J. Pathol."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Khalique, S., Nash, S., Mansfield, D., Wampfler, J., Attygale, A., Vroobel, K., Kemp, H., Buus, R., Cottom, H., and Roxanis, I. (2021). Quantitative assessment and prognostic associations of the immune landscape in ovarian clear cell carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13153854"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.canlet.2019.07.004","article-title":"Low-dose triple drug combination targeting the PI3K\/AKT\/mTOR pathway and the MAPK pathway is an effective approach in ovarian clear cell carcinoma","volume":"461","author":"Caumanns","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_191","first-page":"1982","article-title":"Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro","volume":"55","author":"Shi","year":"1995","journal-title":"Cancer Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"4261","DOI":"10.1158\/1078-0432.CCR-06-2770","article-title":"RAD001 inhibits human ovarian cancer cell proliferation, enhances cisplatin-induced apoptosis, and prolongs survival in an ovarian cancer model","volume":"13","author":"Mabuchi","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"113874","DOI":"10.18632\/oncotarget.23022","article-title":"Evaluation of the combination of the dual m-TORC1\/2 inhibitor vistusertib (AZD2014) and paclitaxel in ovarian cancer models","volume":"8","author":"Thavasu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s13402-020-00514-8","article-title":"The PI3K\/mTOR dual inhibitor GSK458 potently impedes ovarian cancer tumorigenesis and metastasis","volume":"43","author":"Xiao","year":"2020","journal-title":"Cell. Oncol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ygyno.2021.07.008","article-title":"The effectiveness of monotherapy with PI3K\/AKT\/mTOR pathway inhibitors in ovarian cancer: A meta-analysis","volume":"163","author":"Uittenboogaard","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.2217\/fon-2022-0666","article-title":"EPIK-O\/ENGOT-OV61: Alpelisib plus olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study)","volume":"18","author":"Cruz","year":"2022","journal-title":"Futur. Oncol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1186\/s13063-022-06201-3","article-title":"DICE: Dual mTorc Inhibition in advanCed\/recurrent Epithelial ovarian cancer resistant to standard treatment\u2014A study protocol for a randomised trial investigating a novel therapy called TAK228","volume":"23","author":"Fiorentino","year":"2022","journal-title":"Trials"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1093\/bib\/bby026","article-title":"Molecular subtyping of cancer: Current status and moving toward clinical applications","volume":"20","author":"Zhao","year":"2018","journal-title":"Brief. Bioinform."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"EVIDoa2200282","DOI":"10.1056\/EVIDoa2200282","article-title":"Validation of a Salivary miRNA Signature of Endometriosis\u2014Interim Data","volume":"2","author":"Bendifallah","year":"2023","journal-title":"NEJM Evid."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.semcancer.2019.05.012","article-title":"Role of the PI3K\/AKT\/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance","volume":"59","author":"Ediriweera","year":"2019","journal-title":"Semin. Cancer Biol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/2160\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:54:33Z","timestamp":1760108073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/2160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,6]]},"references-count":200,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["cancers16112160"],"URL":"https:\/\/doi.org\/10.3390\/cancers16112160","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,6]]}}}