oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2023-22-5-118-133oncotomsk-2766Research ArticleОБЗОРЫREVIEWSДиагностика и лечение рака яичников в свете современных молекулярно-генетических достиженийDiagnosis and treatment of ovarian cancer in the light of modern molecular genetic achievementshttps://orcid.org/0000-0003-0882-7048КагироваЭ. М.KagirovaE. M.

Кагирова Эвелина Марсельевна - младший научный сотрудник лаборатории молекулярной генетики Института урологии и клинической онкологии.

450008, Уфа, ул. Ленина, 3

Rita I. Khusainova - DSc, Associate Professor, Professor of the Department of Medical Genetics and Fundamental Medicine, Bashkir SMU MHR; Leading Researcher of the Institute of Biochemistry and Genetics, Ufa FRC RAS. Researcher ID (WOS): E-6061-2014.

3, Lenin st., Ufa, 450008

evelina.kagirova@mail.ruhttps://orcid.org/0000-0002-8643-850XХусаиноваР. И.KhusainovaR. I.

Хусаинова Рита Игоревна - доктор биологических наук, доцент, профессор кафедры медицинской генетики и фундаментальной медицины, ФГБОУ ВО «Башкирский ГМУ» Минздрава России; главный научный сотрудник, ГНЦ РФ ФГБУ «НМИЦЭ» Минздрава России. Researcher ID (WOS): E-6061-2014.

450008, Уфа, ул. Ленина, 3; 115478, г. Москва, ул. Дмитрия Ульянова, 112

Rita I. Khusainova - DSc, Associate Professor, Professor of the Department of Medical Genetics and Fundamental Medicine, Bashkir SMU MHR; Leading Researcher of the Institute of Biochemistry and Genetics, Ufa FRC RAS. Researcher ID (WOS): E-6061-2014.

3, Lenin st., Ufa, 450008; 71, October ave., Ufa, 450054

https://orcid.org/0000-0002-7045-8215МинниахметовИ. Р.MinniakhmetovI. R.

Минниахметов Илдар Рамилевич, кандидат биологических наук, доцент кафедры медицинской генетики и фундаментальной медицины, ФГБОУ ВО «Башкирский ГМУ» Минздрава России; заведующий лабораторией геномной медицины, ГНЦ РФ ФГБУ «НМИЦЭ» Минздрава России. Researcher ID (WOS): ААТ-8799-2021.

450008, Уфа, ул. Ленина, 3; 115478, г. Москва, ул. Дмитрия Ульянова, 11

Ildar R. Minniakhmetov - PhD, Associate Professor of the Department of Medical Genetics and Fundamental Medicine, Bashkir SMU MHR. Researcher ID (WOS): ААТ-8799-2021.

3, Lenin st., Ufa, 450008; 71, October ave., Ufa, 450054

ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава РоссииРоссияBashkir state medical university of the Ministry of Health of RussiaRussian FederationФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России; ГНЦ РФ ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава РоссииРоссияBashkir state medical university of the Ministry of Health of Russia; Ufa Federal Research Center of the Russian Academy of SciencesRussian Federation202315112023225118133Copyright © Кагирова Э.М., Хусаинова Р.И., Минниахметов И.Р., 20232023Кагирова Э.М., Хусаинова Р.И., Минниахметов И.Р.Kagirova E.M., Khusainova R.I., Minniakhmetov I.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2766

Цель исследования – систематизация и обобщение литературных данных по изучению клиникогенетических аспектов, молекулярного патогенеза, а также новых тенденций диагностики и лечения злокачественных новообразований яичников.

Материал и методы

Материал и методы. Поиск литературных источников производился по базам данных Web of science, scopus, medline, pubmed, elibrary.

Результаты

Результаты. Рак яичников занимает 1-е место в структуре смертности среди гинекологических злокачественных новообразований и является гетерогенной группой опухолей, каждая из которых имеет различия в патогенезе, спектре и частоте мутаций вовлеченных генов, ответе на терапию и прогнозе течения заболевания. Более 80 % всех злокачественных опухолей яичников имеют эпителиальное происхождение (карциномы), около 26 % всех случаев рака яичников обусловлены герминальными мутациями, встречающимися в генах BRСА1/BRCA2. Приоритетными направлениями в изучении рака яичников являются совершенствование методов диагностики, алгоритма обследования, выявление новых биомаркеров, изучение микроокружения опухоли и состава асцитической жидкости для выявления рака на ранних стадиях и назначения соответствующей терапии. Благодаря современным терапевтическим агентам, основанным на молекулярном профиле опухоли, стало возможным персонифицировать лечение и повысить его эффективность. Достижения молекулярно-генетических, цитологических, иммунологических и биохимических исследований способствуют формированию современных подходов к диагностике и лечению рака яичников.

Заключение

Заключение. Зарубежные и отечественные работы содержат сведения по данной проблеме и дают возможность оценить современные подходы в диагностике и лечении рака яичников. С появлением новых данных становятся более понятными клеточный состав и роль микроокружения опухоли в появлении резистентности к той или иной терапии. Появляются новые биомаркеры, которые помогут выявить наилучших кандидатов для лечения рака яичников. Необходимо продолжать фундаментальные и прикладные исследования по изучению возможностей применения различных диагностических и терапевтических агентов при раке яичников.

The purpose of the study was to systematize and summarize the literature data on the study of clinical and genetic aspects, molecular pathogenesis, as well as new trends in the diagnosis and treatment of ovarian cancer.

Material and Methods

Material and Methods. A literature search was conducted using Web of science, scopus, medline, pubmed, and elibrary databases.

Results

Results. Ovarian cancer is the leading cause of death in women diagnosed with gynecological cancer. ovarian cancer is a heterogeneous disease composed of different types of tumors, each of which has differences in pathogenesis, spectrum and mutation frequencies in characteristic genes, response to therapy and prognosis of the disease. more than 80 % of all malignant ovarian tumors are of epithelial origin (carcinomas) and about 26 % of all cases of ovarian cancer are caused by germline mutations found in the BRCA1/BRCA2 genes. to date, the priority areas in the study of ovarian cancer are the improvement of diagnostic methods, algorithm of examination of women, identification of new biomarkers, study of tumor microenvironment and composition of ascitic fluid to detect cancer at early stages and prescribe appropriate therapy. Recent advances in targeted therapy based on the molecular profile of the tumor have made it possible to personalize treatment and increase its effectiveness. Achievements in molecular genetic, cytological, immunological and biochemical studies contribute to the development of novel approaches to the diagnosis and treatment of ovarian cancer.

Conclusion

Conclusion. With the advent of new novel approaches to the diagnosis and treatment of ovarian cancer, it is becoming increasingly clear that the tumor microenvironment can significantly affect the success of chemotherapy. New biomarkers can help identify the best candidates for ovarian cancer treatment. Further basic and applied research is needed to explore the use of different diagnostic and therapeutic agents in ovarian cancer.

рак яичниковмутацииBRCA1BRCA2таргетная терапиямикроокружение опухолиovarian cancermutationsBRCA1BRCA2targeted therapytumour microenvironmentReferencesWorld ovarian cancer coalition [Internet]. Ovarian cancer [cited 2023 Feb 01]. URL: https://worldovariancancercoalition.org/aboutovarian-cancer/key-stats.World ovarian cancer coalition [Internet]. Ovarian cancer [cited 2023 Feb 01]. URL: https://worldovariancancercoalition.org/aboutovarian-cancer/key-stats.Jemal A., Bray F., Center M.M., Ferlay J., Ward E., Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61(2): 69–90. doi: 10.3322/caac.20107. Erratum in: CA Cancer J Clin. 2011; 61(2): 134.Jemal A., Bray F., Center M.M., Ferlay J., Ward E., Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61(2): 69–90. doi: 10.3322/caac.20107. Erratum in: CA Cancer J Clin. 2011; 61(2): 134.Vaughan S., Coward J.I., Bast R.C., Berchuck A., Berek J.S., Brenton J.D., Coukos G., Crum C.C., Drapkin R., Etemadmoghadam D., Friedlander M., Gabra H., Kaye S.B., Lord C.J., Lengyel E., Levine D.A., McNeish I.A., Menon U., Mills G.B., Nephew K.P., Oza A.M., Sood A.K., Stronach E.A., Walczak H., Bowtell D.D., Balkwill F.R. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011; 11(10): 719–25. doi: 10.1038/nrc3144.Vaughan S., Coward J.I., Bast R.C., Berchuck A., Berek J.S., Brenton J.D., Coukos G., Crum C.C., Drapkin R., Etemadmoghadam D., Friedlander M., Gabra H., Kaye S.B., Lord C.J., Lengyel E., Levine D.A., McNeish I.A., Menon U., Mills G.B., Nephew K.P., Oza A.M., Sood A.K., Stronach E.A., Walczak H., Bowtell D.D., Balkwill F.R. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011; 11(10): 719–25. doi: 10.1038/nrc3144.Состояние онкологической помощи населению России в 2020 году. Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой М., 239 с.The status of cancer care for the population of Russia in 2020. Ed. by A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow, 2021. 239 p. (in Russian).Blagden S.P. Harnessing Pandemonium: The Clinical Implications of Tumor Heterogeneity in Ovarian Cancer. Front Oncol. 2015; 5: 149. doi: 10.3389/fonc.2015.00149.Blagden S.P. Harnessing Pandemonium: The Clinical Implications of Tumor Heterogeneity in Ovarian Cancer. Front Oncol. 2015; 5: 149. doi: 10.3389/fonc.2015.00149.Female Genital Tumours: WHO Classification of Tumours. 5th ed.; Vol. 4. IARC: Lyon, France, 2020.Female Genital Tumours: WHO Classification of Tumours. 5th ed.; Vol. 4. IARC: Lyon, France, 2020.Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011; 474(7353): 609–15. doi: 10.1038/nature10166. Erratum in: Nature. 2012; 490(7419): 298.Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011; 474(7353): 609–15. doi: 10.1038/nature10166. Erratum in: Nature. 2012; 490(7419): 298.Ahmed A.A., Etemadmoghadam D., Temple J., Lynch A.G., Riad M., Sharma R., Stewart C., Fereday S., Caldas C., Defazio A., Bowtell D., Brenton J.D. Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol. 2010; 221(1): 49–56. doi: 10.1002/path.2696.Ahmed A.A., Etemadmoghadam D., Temple J., Lynch A.G., Riad M., Sharma R., Stewart C., Fereday S., Caldas C., Defazio A., Bowtell D., Brenton J.D. Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol. 2010; 221(1): 49–56. doi: 10.1002/path.2696.Hollis R.L., Thomson J.P., Stanley B., Churchman M., Meynert A.M., Rye T., Bartos C., IIda Y., Croy I., Mackean M., Nussey F., Okamoto A., Semple C.A., Gourley C., Herrington C.S. Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome. Nat Commun. 2020. 11(1). https://doi.org/10.1038/s41467-020-18819-5.Hollis R.L., Thomson J.P., Stanley B., Churchman M., Meynert A.M., Rye T., Bartos C., IIda Y., Croy I., Mackean M., Nussey F., Okamoto A., Semple C.A., Gourley C., Herrington C.S. Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome. Nat Commun. 2020. 11(1). https://doi.org/10.1038/s41467-020-18819-5.Yamamoto S., Tsuda H., Takano M., Iwaya K., Tamai S., Matsubara O. PIK3CA mutation is an early event in the development of endometriosisassociated ovarian clear cell adenocarcinoma. J Pathol. 2011; 225(2): 189–94. doi: 10.1002/path.2940.Yamamoto S., Tsuda H., Takano M., Iwaya K., Tamai S., Matsubara O. PIK3CA mutation is an early event in the development of endometriosisassociated ovarian clear cell adenocarcinoma. J Pathol. 2011; 225(2): 189–94. doi: 10.1002/path.2940.De Leo A., Santini D., Ceccarelli C., Santandrea G., Palicelli A., Acquaviva G., Chiarucci F., Rosini F., Ravegnini G., Pession A., Turchetti D., Zamagni C., Perrone A.M., De Iaco P., Tallini G., de Biase D. What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors. Diagnostics (Basel). 2021; 11(4): 697. doi: 10.3390/diagnostics11040697.De Leo A., Santini D., Ceccarelli C., Santandrea G., Palicelli A., Acquaviva G., Chiarucci F., Rosini F., Ravegnini G., Pession A., Turchetti D., Zamagni C., Perrone A.M., De Iaco P., Tallini G., de Biase D. What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors. Diagnostics (Basel). 2021; 11(4): 697. doi: 10.3390/diagnostics11040697.Soslow R.A., Han G., Park K.J., Garg K., Olvera N., Spriggs D.R., Kauff N.D., Levine D.A. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol. 2012; 25(4): 625–36. doi: 10.1038/modpathol.2011.183.Soslow R.A., Han G., Park K.J., Garg K., Olvera N., Spriggs D.R., Kauff N.D., Levine D.A. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol. 2012; 25(4): 625–36. doi: 10.1038/modpathol.2011.183.Matias-Guiu X., Stewart C.J.R. Endometriosis-associated ovarian neoplasia. Pathology. 2018; 50(2): 190–204. doi: 10.1016/j.pathol.2017.10.006.Matias-Guiu X., Stewart C.J.R. Endometriosis-associated ovarian neoplasia. Pathology. 2018; 50(2): 190–204. doi: 10.1016/j.pathol.2017.10.006.IIda Y., Okamoto A., Hollis R.L., Gourley C., Herrington C.S. Clear cell carcinoma of the ovary: a clinical and molecular perspective. Int J Gynecol Cancer. 2021; 31(4): 605–16. doi: 10.1136/ijgc-2020-001656.IIda Y., Okamoto A., Hollis R.L., Gourley C., Herrington C.S. Clear cell carcinoma of the ovary: a clinical and molecular perspective. Int J Gynecol Cancer. 2021; 31(4): 605–16. doi: 10.1136/ijgc-2020-001656.Sasamori H., Nakayama K., Razia S., Yamashita H., Ishibashi T., Ishikawa M., Sato S., Nakayama S., Otsuki Y., Fujiwaki R., Ishikawa N., Kyo S. Mutation Profiles of Ovarian Seromucinous Borderline Tumors in Japanese Patients. Curr Oncol. 2022; 29(5): 3658–67. doi: 10.3390/curroncol29050294.Sasamori H., Nakayama K., Razia S., Yamashita H., Ishibashi T., Ishikawa M., Sato S., Nakayama S., Otsuki Y., Fujiwaki R., Ishikawa N., Kyo S. Mutation Profiles of Ovarian Seromucinous Borderline Tumors in Japanese Patients. Curr Oncol. 2022; 29(5): 3658–67. doi: 10.3390/curroncol29050294.Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Amarasinghe K.C., Ananda S., Anglesio M.S., Au-Yeung G., Böhm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.E., Churchman M., DeFazio A., Demeo R., Dudley R., Fairweather N., Fedele C.G., Fereday S., Fox S.B., Gilks C.B., Gorringe K.L. The molecular origin and taxonomy of mucinous ovarian carcinoma. Nat Commun. 2019; 10(1).Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Amarasinghe K.C., Ananda S., Anglesio M.S., Au-Yeung G., Böhm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.E., Churchman M., DeFazio A., Demeo R., Dudley R., Fairweather N., Fedele C.G., Fereday S., Fox S.B., Gilks C.B., Gorringe K.L. The molecular origin and taxonomy of mucinous ovarian carcinoma. Nat Commun. 2019; 10(1).Samuel D., Diaz-Barbe A., Pinto A., Schlumbrecht M., George S. Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2. Cells. 2022; 11(3): 539. doi: 10.3390/cells11030539.Samuel D., Diaz-Barbe A., Pinto A., Schlumbrecht M., George S. Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2. Cells. 2022; 11(3): 539. doi: 10.3390/cells11030539.Jiang X., Li X., Li W., Bai H., Zhang Z. PARP inhibitors in ovarian cancer: Sensitivity prediction and resistance mechanisms. J Cell Mol Med. 2019; 23(4): 2303–13. doi: 10.1111/jcmm.14133.Jiang X., Li X., Li W., Bai H., Zhang Z. PARP inhibitors in ovarian cancer: Sensitivity prediction and resistance mechanisms. J Cell Mol Med. 2019; 23(4): 2303–13. doi: 10.1111/jcmm.14133.Altman A.D., Nelson G.S., Ghatage P., McIntyre J.B., Capper D., Chu P., Nation J.G., Karnezis A.N., Han G., Kalloger S.E., Köbel M. The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors. Mod Pathol. 2013; 26(9): 1255–63. doi: 10.1038/modpathol.2013.55.Altman A.D., Nelson G.S., Ghatage P., McIntyre J.B., Capper D., Chu P., Nation J.G., Karnezis A.N., Han G., Kalloger S.E., Köbel M. The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors. Mod Pathol. 2013; 26(9): 1255–63. doi: 10.1038/modpathol.2013.55.Santandrea G., Piana S., Valli R., Zanelli M., Gasparini E., De Leo A., Mandato V.D., Palicelli A. Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature. Diagnostics (Basel). 2021; 11(2): 199. doi: 10.3390/diagnostics11020199.Santandrea G., Piana S., Valli R., Zanelli M., Gasparini E., De Leo A., Mandato V.D., Palicelli A. Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature. Diagnostics (Basel). 2021; 11(2): 199. doi: 10.3390/diagnostics11020199.Konstantinopoulos P.A., Ceccaldi R., Shapiro G.I., D’Andrea A.D. Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discov. 2015; 5(11): 1137–54. doi: 10.1158/2159-8290.CD-15-0714.Konstantinopoulos P.A., Ceccaldi R., Shapiro G.I., D’Andrea A.D. Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discov. 2015; 5(11): 1137–54. doi: 10.1158/2159-8290.CD-15-0714.Mekonnen N., Yang H., Shin Y.K. Homologous Recombination Deficiency in Ovarian, Breast, Colorectal, Pancreatic, Non-Small Cell Lung and Prostate Cancers, and the Mechanisms of Resistance to PARP Inhibitors. Front Oncol. 2022; 12. doi: 10.3389/fonc.2022.880643.Mekonnen N., Yang H., Shin Y.K. Homologous Recombination Deficiency in Ovarian, Breast, Colorectal, Pancreatic, Non-Small Cell Lung and Prostate Cancers, and the Mechanisms of Resistance to PARP Inhibitors. Front Oncol. 2022; 12. doi: 10.3389/fonc.2022.880643.Talens F., Jalving M., Gietema J.A., Van Vugt M.A. Therapeutic targeting and patient selection for cancers with homologous recombination defects. Expert Opin Drug Discov. 2017; 12(6): 565–81. doi: 10.1080/17460441.2017.1322061.Talens F., Jalving M., Gietema J.A., Van Vugt M.A. Therapeutic targeting and patient selection for cancers with homologous recombination defects. Expert Opin Drug Discov. 2017; 12(6): 565–81. doi: 10.1080/17460441.2017.1322061.Konstantinopoulos P.A., Lacchetti C., Annunziata C.M. Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline Summary. JCO Oncol Pract. 2020; 16(8): 835–8. doi: 10.1200/jOP.19.00773.Konstantinopoulos P.A., Lacchetti C., Annunziata C.M. Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline Summary. JCO Oncol Pract. 2020; 16(8): 835–8. doi: 10.1200/jOP.19.00773.Zamarin D. Novel therapeutics: response and resistance in ovarian cancer. Int J Gynecol Cancer. 2019; 29(s2): 16–21. doi: 10.1136/ijgc-2019-000456.Zamarin D. Novel therapeutics: response and resistance in ovarian cancer. Int J Gynecol Cancer. 2019; 29(s2): 16–21. doi: 10.1136/ijgc-2019-000456.Wang H., Liu P., Xu H., Dai H. Early diagonosis of ovarian cancer: serum HE4, CA125 and ROMA model. Am J Transl Res. 2021; 13(12): 14141–8.Wang H., Liu P., Xu H., Dai H. Early diagonosis of ovarian cancer: serum HE4, CA125 and ROMA model. Am J Transl Res. 2021; 13(12): 14141–8.Yang W.L., Gentry-Maharaj A., Simmons A., Ryan A., Fourkala E.O., Lu Z., Baggerly K.A., Zhao Y., Lu K.H., Bowtell D., Jacobs I., Skates S.J., He W.W., Menon U., Bast R.C.; AOCS Study Group. Elevation of TP53 Autoantibody Before CA125 in Preclinical Invasive Epithelial Ovarian Cancer. Clin Cancer Res. 2017; 23(19): 5912–22. doi: 10.1158/1078-0432.CCR-17-0284.Yang W.L., Gentry-Maharaj A., Simmons A., Ryan A., Fourkala E.O., Lu Z., Baggerly K.A., Zhao Y., Lu K.H., Bowtell D., Jacobs I., Skates S.J., He W.W., Menon U., Bast R.C.; AOCS Study Group. Elevation of TP53 Autoantibody Before CA125 in Preclinical Invasive Epithelial Ovarian Cancer. Clin Cancer Res. 2017; 23(19): 5912–22. doi: 10.1158/1078-0432.CCR-17-0284.Dochez V., Caillon H., Vaucel E., Dimet J., Winer N., Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res. 2019; 12(1). doi: 10.1186/s13048-019-0503-7.Dochez V., Caillon H., Vaucel E., Dimet J., Winer N., Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res. 2019; 12(1). doi: 10.1186/s13048-019-0503-7.Yang W.L., Lu Z., Bast R.C. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn. 2017; 17(6): 577–91. doi: 10.1080/14737159.2017.1326820.Yang W.L., Lu Z., Bast R.C. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn. 2017; 17(6): 577–91. doi: 10.1080/14737159.2017.1326820.Terry K.L., Schock H., Fortner R.T., Hüsing A., Fichorova R.N., Yamamoto H.S., Vitonis A.F., Johnson T., Overvad K., Tjønneland A., BoutronRuault M.C., Mesrine S., Severi G., Dossus L., Rinaldi S., Boeing H., Benetou V., Lagiou P., Trichopoulou A., Krogh V., Kuhn E., Panico S., Bueno-de-Mesquita H.B., Onland-Moret N.C., Peeters P.H., Gram I.T., Weiderpass E., Duell E.J., Sanchez M.J., Ardanaz E., Etxezarreta N., Navarro C., Idahl A., Lundin E., Jirström K., Manjer J., Wareham N.J., Khaw K.T., Byrne K.S., Travis R.C., Gunter M.J., Merritt M.A., Riboli E., Cramer D.W., Kaaks R. A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort. Clin Cancer Res. 2016; 22(18): 4664–75. doi: 10.1158/1078-0432.CCR-16-0316.Terry K.L., Schock H., Fortner R.T., Hüsing A., Fichorova R.N., Yamamoto H.S., Vitonis A.F., Johnson T., Overvad K., Tjønneland A., BoutronRuault M.C., Mesrine S., Severi G., Dossus L., Rinaldi S., Boeing H., Benetou V., Lagiou P., Trichopoulou A., Krogh V., Kuhn E., Panico S., Bueno-de-Mesquita H.B., Onland-Moret N.C., Peeters P.H., Gram I.T., Weiderpass E., Duell E.J., Sanchez M.J., Ardanaz E., Etxezarreta N., Navarro C., Idahl A., Lundin E., Jirström K., Manjer J., Wareham N.J., Khaw K.T., Byrne K.S., Travis R.C., Gunter M.J., Merritt M.A., Riboli E., Cramer D.W., Kaaks R. A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort. Clin Cancer Res. 2016; 22(18): 4664–75. doi: 10.1158/1078-0432.CCR-16-0316.Kim B., Park Y., Kim B., Ahn H.J., Lee K.A., Chung J.E., Han S.W. Diagnostic performance of CA 125, HE4, and risk of Ovarian Malignancy Algorithm for ovarian cancer. J Clin Lab Anal. 2019; 33(1). doi: 10.1002/jcla.22624.Kim B., Park Y., Kim B., Ahn H.J., Lee K.A., Chung J.E., Han S.W. Diagnostic performance of CA 125, HE4, and risk of Ovarian Malignancy Algorithm for ovarian cancer. J Clin Lab Anal. 2019; 33(1). doi: 10.1002/jcla.22624.Zhang R., Siu M.K.Y., Ngan H.Y.S., Chan K.K.L. Molecular Biomarkers for the Early Detection of Ovarian Cancer. Int J Mol Sci. 2022; 23(19): 12041. doi: 10.3390/ijms231912041.Zhang R., Siu M.K.Y., Ngan H.Y.S., Chan K.K.L. Molecular Biomarkers for the Early Detection of Ovarian Cancer. Int J Mol Sci. 2022; 23(19): 12041. doi: 10.3390/ijms231912041.Macdonald I.K., Parsy-Kowalska C.B., Chapman C.J. Autoantibodies: Opportunities for Early Cancer Detection. Trends Cancer. 2017; 3(3): 198–213. doi: 10.1016/j.trecan.2017.02.003.Macdonald I.K., Parsy-Kowalska C.B., Chapman C.J. Autoantibodies: Opportunities for Early Cancer Detection. Trends Cancer. 2017; 3(3): 198–213. doi: 10.1016/j.trecan.2017.02.003.Fortner R.T., Damms-Machado A., Kaaks R. Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection. Gynecol Oncol. 2017; 147(2): 465–80. doi: 10.1016/j.ygyno.2017.07.138.Fortner R.T., Damms-Machado A., Kaaks R. Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection. Gynecol Oncol. 2017; 147(2): 465–80. doi: 10.1016/j.ygyno.2017.07.138.Lokshin A.E., Winans M., Landsittel D., Marrangoni A.M., Velikokhatnaya L., Modugno F., Nolen B.M., Gorelik E. Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer. Gynecol Oncol. 2006; 102(2): 244–51. doi: 10.1016/j.ygyno.2005.12.011.Lokshin A.E., Winans M., Landsittel D., Marrangoni A.M., Velikokhatnaya L., Modugno F., Nolen B.M., Gorelik E. Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer. Gynecol Oncol. 2006; 102(2): 244–51. doi: 10.1016/j.ygyno.2005.12.011.Nakamura K., Sawada K., Yoshimura A., Kinose Y., Nakatsuka E., Kimura T. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer. 2016; 15(1): 48. doi: 10.1186/s12943-016-0536-0.Nakamura K., Sawada K., Yoshimura A., Kinose Y., Nakatsuka E., Kimura T. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer. 2016; 15(1): 48. doi: 10.1186/s12943-016-0536-0.Yokoi A., Yoshioka Y., Hirakawa A., Yamamoto Y., Ishikawa M., Ikeda S.I., Kato T., NIImi K., Kajiyama H., Kikkawa F., Ochiya T. A combination of circulating miRNAs for the early detection of ovarian cancer. Oncotarget. 2017; 8(52): 89811–23. doi: 10.18632/oncotarget.20688.Yokoi A., Yoshioka Y., Hirakawa A., Yamamoto Y., Ishikawa M., Ikeda S.I., Kato T., NIImi K., Kajiyama H., Kikkawa F., Ochiya T. A combination of circulating miRNAs for the early detection of ovarian cancer. Oncotarget. 2017; 8(52): 89811–23. doi: 10.18632/oncotarget.20688.Cheng X., Zhang L., Chen Y., Qing C. Circulating cell-free DNA and circulating tumor cells, the “liquid biopsies” in ovarian cancer. J Ovarian Res. 2017; 10(1): 75. doi: 10.1186/s13048-017-0369-5.Cheng X., Zhang L., Chen Y., Qing C. Circulating cell-free DNA and circulating tumor cells, the “liquid biopsies” in ovarian cancer. J Ovarian Res. 2017; 10(1): 75. doi: 10.1186/s13048-017-0369-5.Elias K.M., Guo J., Bast R.C. Early Detection of Ovarian Cancer. Hematol Oncol Clin North Am. 2018; 32(6): 903–14. doi: 10.1016/j.hoc.2018.07.003.Elias K.M., Guo J., Bast R.C. Early Detection of Ovarian Cancer. Hematol Oncol Clin North Am. 2018; 32(6): 903–14. doi: 10.1016/j.hoc.2018.07.003.Arneth B. Update on the types and usage of liquid biopsies in the clinical setting: a systematic review. BMC Cancer. 2018; 18(1): 527. doi: 10.1186/s12885-018-4433-3.Arneth B. Update on the types and usage of liquid biopsies in the clinical setting: a systematic review. BMC Cancer. 2018; 18(1): 527. doi: 10.1186/s12885-018-4433-3.Yang Z., Wang W., Zhao L., Wang X., Gimple R.C., Xu L., Wang Y., Rich J.N., Zhou S. Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs. Sci Adv. 2021; 7(9). doi: 10.1126/sciadv.abb0737.Yang Z., Wang W., Zhao L., Wang X., Gimple R.C., Xu L., Wang Y., Rich J.N., Zhou S. Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs. Sci Adv. 2021; 7(9). doi: 10.1126/sciadv.abb0737.Cohen J.D., Li L., Wang Y., Thoburn C., Afsari B., Danilova L., Douville C., Javed A.A., Wong F., Mattox A., Hruban R.H., Wolfgang C.L., Goggins M.G., Dal Molin M., Wang T.L., Roden R., Klein A.P., Ptak J., Dobbyn L., Schaefer J., Silliman N., Popoli M., Vogelstein J.T., Browne J.D., Schoen R.E., Brand R.E., Tie J., Gibbs P., Wong H.L., Mansfield A.S., Jen J., Hanash S.M., Falconi M., Allen P.J., Zhou S., Bettegowda C., Diaz L.A., Tomasetti C., Kinzler K.W., Vogelstein B., Lennon A.M., Papadopoulos N. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018; 359(6378): 926–30. doi: 10.1126/science.aar3247.Cohen J.D., Li L., Wang Y., Thoburn C., Afsari B., Danilova L., Douville C., Javed A.A., Wong F., Mattox A., Hruban R.H., Wolfgang C.L., Goggins M.G., Dal Molin M., Wang T.L., Roden R., Klein A.P., Ptak J., Dobbyn L., Schaefer J., Silliman N., Popoli M., Vogelstein J.T., Browne J.D., Schoen R.E., Brand R.E., Tie J., Gibbs P., Wong H.L., Mansfield A.S., Jen J., Hanash S.M., Falconi M., Allen P.J., Zhou S., Bettegowda C., Diaz L.A., Tomasetti C., Kinzler K.W., Vogelstein B., Lennon A.M., Papadopoulos N. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018; 359(6378): 926–30. doi: 10.1126/science.aar3247.Bartlett T.E., Chindera K., McDermott J., Breeze C.E., Cooke W.R., Jones A., Reisel D., Karegodar S.T., Arora R., Beck S., Menon U., Dubeau L., Widschwendter M. Epigenetic reprogramming of fallopian tube fimbriae in BRCA mutation carriers defines early ovarian cancer evolution. Nat Commun. 2016; 7: 11620. doi: 10.1038/ncomms11620.Bartlett T.E., Chindera K., McDermott J., Breeze C.E., Cooke W.R., Jones A., Reisel D., Karegodar S.T., Arora R., Beck S., Menon U., Dubeau L., Widschwendter M. Epigenetic reprogramming of fallopian tube fimbriae in BRCA mutation carriers defines early ovarian cancer evolution. Nat Commun. 2016; 7: 11620. doi: 10.1038/ncomms11620.Natanzon Y., Goode E.L., Cunningham J.M. Epigenetics in ovarian cancer. Semin Cancer Biol. 2018; 51: 160–9. doi: 10.1016/j.semcancer.2017.08.003.Natanzon Y., Goode E.L., Cunningham J.M. Epigenetics in ovarian cancer. Semin Cancer Biol. 2018; 51: 160–9. doi: 10.1016/j.semcancer.2017.08.003.Talens R.P., Boomsma D.I., Tobi E.W., Kremer D., Jukema J.W., Willemsen G., Putter H., Slagboom P.E., Heijmans B.T. Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J. 2010; 24(9): 3135–44. doi: 10.1096/fj.09-150490.Talens R.P., Boomsma D.I., Tobi E.W., Kremer D., Jukema J.W., Willemsen G., Putter H., Slagboom P.E., Heijmans B.T. Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J. 2010; 24(9): 3135–44. doi: 10.1096/fj.09-150490.Абрамов П.М., Винокурова С.В., Елкин Д.С. Маркеры метилирования ДНК для диагностики серозного рака яичников. Онкогинекология. 2019; 4(32): 4–16.Abramov P.M., Vinokurova S.V., Elkin D.S. DNA Methylation Markers For Diagnosis Of Serous Ovarian Cancer. Oncogynecology. 2019; 4(32): 4–16. (in Russian).Loginov V.I., Pronina I.V., Filippova E.A., Burdennyy A.M., Lukina S.S., Kazubskaya T.P., Uroshlev L.A., Fridman M.V., Brovkina O.I., Apanovich N.V., Karpukhin A.V., Stilidi I.S., KushlinskII N.E., Dmitriev A.A., Braga E.A. Aberrant Methylation of 20 miRNA Genes Specifically Involved in Various Steps of Ovarian Carcinoma Spread: From Primary Tumors to Peritoneal Macroscopic Metastases. Int J Mol Sci. 2022; 23(3): 1300. doi: 10.3390/ijms23031300.Loginov V.I., Pronina I.V., Filippova E.A., Burdennyy A.M., Lukina S.S., Kazubskaya T.P., Uroshlev L.A., Fridman M.V., Brovkina O.I., Apanovich N.V., Karpukhin A.V., Stilidi I.S., KushlinskII N.E., Dmitriev A.A., Braga E.A. Aberrant Methylation of 20 miRNA Genes Specifically Involved in Various Steps of Ovarian Carcinoma Spread: From Primary Tumors to Peritoneal Macroscopic Metastases. Int J Mol Sci. 2022; 23(3): 1300. doi: 10.3390/ijms23031300.Bondurant A.E., Huang Z., Whitaker R.S., Simel L.R., Berchuck A., Murphy S.K. Quantitative detection of RASSF1A DNA promoter methylation in tumors and serum of patients with serous epithelial ovarian cancer. Gynecol Oncol. 2011; 123(3): 581–7. doi: 10.1016/j.ygyno.2011.08.029.Bondurant A.E., Huang Z., Whitaker R.S., Simel L.R., Berchuck A., Murphy S.K. Quantitative detection of RASSF1A DNA promoter methylation in tumors and serum of patients with serous epithelial ovarian cancer. Gynecol Oncol. 2011; 123(3): 581–7. doi: 10.1016/j.ygyno.2011.08.029.Fiegl H., Windbichler G., Mueller-Holzner E., Goebel G., Lechner M., Jacobs I.J., Widschwendter M. HOXA11 DNA methylation--a novel prognostic biomarker in ovarian cancer. Int J Cancer. 2008; 123(3): 725–9. doi: 10.1002/ijc.23563.Fiegl H., Windbichler G., Mueller-Holzner E., Goebel G., Lechner M., Jacobs I.J., Widschwendter M. HOXA11 DNA methylation--a novel prognostic biomarker in ovarian cancer. Int J Cancer. 2008; 123(3): 725–9. doi: 10.1002/ijc.23563.Xiao Y., Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 2021; 221. doi: 10.1016/j.pharmthera.2020.107753.Xiao Y., Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 2021; 221. doi: 10.1016/j.pharmthera.2020.107753.Zheng G.X., Terry J.M., Belgrader P., Ryvkin P., Bent Z.W., Wilson R., Ziraldo S.B., Wheeler T.D., McDermott G.P., Zhu J., Gregory M.T., Shuga J., Montesclaros L., Underwood J.G., Masquelier D.A., Nishimura S.Y., Schnall-Levin M., Wyatt P.W., Hindson C.M., Bharadwaj R., Wong A., Ness K.D., Beppu L.W., Deeg H.J., McFarland C., Loeb K.R., Valente W.J., Ericson N.G., Stevens E.A., Radich J.P., Mikkelsen T.S., Hindson B.J., Bielas J.H. Massively parallel digital transcriptional profiling of single cells. Nat Commun. 2017; 8. doi: 10.1038/ncomms14049.Zheng G.X., Terry J.M., Belgrader P., Ryvkin P., Bent Z.W., Wilson R., Ziraldo S.B., Wheeler T.D., McDermott G.P., Zhu J., Gregory M.T., Shuga J., Montesclaros L., Underwood J.G., Masquelier D.A., Nishimura S.Y., Schnall-Levin M., Wyatt P.W., Hindson C.M., Bharadwaj R., Wong A., Ness K.D., Beppu L.W., Deeg H.J., McFarland C., Loeb K.R., Valente W.J., Ericson N.G., Stevens E.A., Radich J.P., Mikkelsen T.S., Hindson B.J., Bielas J.H. Massively parallel digital transcriptional profiling of single cells. Nat Commun. 2017; 8. doi: 10.1038/ncomms14049.Olalekan S., Xie B., Back R., Eckart H., Basu A. Characterizing the tumor microenvironment of metastatic ovarian cancer by single-cell transcriptomics. Cell Rep. 2021; 35(8). doi: 10.1016/j.celrep.2021.109165.Olalekan S., Xie B., Back R., Eckart H., Basu A. Characterizing the tumor microenvironment of metastatic ovarian cancer by single-cell transcriptomics. Cell Rep. 2021; 35(8). doi: 10.1016/j.celrep.2021.109165.Izar B., Tirosh I., Stover E.H., Wakiro I., Cuoco M.S., Alter I., Rodman C., Leeson R., Su M.J., Shah P., Iwanicki M., Walker S.R., Kanodia A., Melms J.C., Mei S., Lin J.R., Porter C.B.M., Slyper M., Waldman J., Jerby-Arnon L., Ashenberg O., Brinker T.J., Mills C., Rogava M., Vigneau S., Sorger P.K., Garraway L.A., Konstantinopoulos P.A., Liu J.F., Matulonis U., Johnson B.E., Rozenblatt-Rosen O., Rotem A., Regev A. A single-cell landscape of high-grade serous ovarian cancer. Nat Med. 2020; 26(8): 1271–9. doi: 10.1038/s41591-020-0926-0.Izar B., Tirosh I., Stover E.H., Wakiro I., Cuoco M.S., Alter I., Rodman C., Leeson R., Su M.J., Shah P., Iwanicki M., Walker S.R., Kanodia A., Melms J.C., Mei S., Lin J.R., Porter C.B.M., Slyper M., Waldman J., Jerby-Arnon L., Ashenberg O., Brinker T.J., Mills C., Rogava M., Vigneau S., Sorger P.K., Garraway L.A., Konstantinopoulos P.A., Liu J.F., Matulonis U., Johnson B.E., Rozenblatt-Rosen O., Rotem A., Regev A. A single-cell landscape of high-grade serous ovarian cancer. Nat Med. 2020; 26(8): 1271–9. doi: 10.1038/s41591-020-0926-0.Sun Y., Wu L., Zhong Y., Zhou K., Hou Y., Wang Z., Zhang Z., Xie J., Wang C., Chen D., Huang Y., Wei X., Shi Y., Zhao Z., Li Y., Guo Z., Yu Q., Xu L., Volpe G., Qiu S., Zhou J., Ward C., Sun H., Yin Y., Xu X., Wang X., Esteban M.A., Yang H., Wang J., Dean M., Zhang Y., Liu S., Yang X., Fan J. Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma. Cell. 2021; 184(2): 404–21. doi: 10.1016/j.cell.2020.11.041.Sun Y., Wu L., Zhong Y., Zhou K., Hou Y., Wang Z., Zhang Z., Xie J., Wang C., Chen D., Huang Y., Wei X., Shi Y., Zhao Z., Li Y., Guo Z., Yu Q., Xu L., Volpe G., Qiu S., Zhou J., Ward C., Sun H., Yin Y., Xu X., Wang X., Esteban M.A., Yang H., Wang J., Dean M., Zhang Y., Liu S., Yang X., Fan J. Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma. Cell. 2021; 184(2): 404–21. doi: 10.1016/j.cell.2020.11.041.Zhou Y., Yang D., Yang Q., Lv X., Huang W., Zhou Z., Wang Y., Zhang Z., Yuan T., Ding X., Tang L., Zhang J., Yin J., Huang Y., Yu W., Wang Y., Zhou C., Su Y., He A., Sun Y., Shen Z., Qian B., Meng W., Fei J., Yao Y., Pan X., Chen P., Hu H. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma. Nat Commun. 2020; 11(1): 6322. doi: 10.1038/s41467-020-20059-6. Erratum in: Nat Commun. 2021; 12(1): 2567.Zhou Y., Yang D., Yang Q., Lv X., Huang W., Zhou Z., Wang Y., Zhang Z., Yuan T., Ding X., Tang L., Zhang J., Yin J., Huang Y., Yu W., Wang Y., Zhou C., Su Y., He A., Sun Y., Shen Z., Qian B., Meng W., Fei J., Yao Y., Pan X., Chen P., Hu H. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma. Nat Commun. 2020; 11(1): 6322. doi: 10.1038/s41467-020-20059-6. Erratum in: Nat Commun. 2021; 12(1): 2567.Larionova I., Tuguzbaeva G., Ponomaryova A., Stakheyeva M., Cherdyntseva N., Pavlov V., Choinzonov E., Kzhyshkowska J. Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers. Front Oncol. 2020; 10. doi: 10.3389/fonc.2020.566511.Larionova I., Tuguzbaeva G., Ponomaryova A., Stakheyeva M., Cherdyntseva N., Pavlov V., Choinzonov E., Kzhyshkowska J. Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers. Front Oncol. 2020; 10. doi: 10.3389/fonc.2020.566511.Chávez-Galán L., Olleros M.L., Vesin D., Garcia I. Much More than M1 and M2 Macrophages, There are also CD169(+) and TCR(+) Macrophages. Front Immunol. 2015; 6: 263. doi: 10.3389/fimmu.2015.00263.Chávez-Galán L., Olleros M.L., Vesin D., Garcia I. Much More than M1 and M2 Macrophages, There are also CD169(+) and TCR(+) Macrophages. Front Immunol. 2015; 6: 263. doi: 10.3389/fimmu.2015.00263.Montfort A., Barker-Clarke R.J., Piskorz A.M., Supernat A., Moore L., Al-Khalidi S., Böhm S., Pharoah P., McDermott J., Balkwill F.R., Brenton J.D. Combining measures of im mune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma. Br J Cancer. 2020; 122(12): 1803–10. doi: 10.1038/s41416-020-0822-x.Montfort A., Barker-Clarke R.J., Piskorz A.M., Supernat A., Moore L., Al-Khalidi S., Böhm S., Pharoah P., McDermott J., Balkwill F.R., Brenton J.D. Combining measures of im mune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma. Br J Cancer. 2020; 122(12): 1803–10. doi: 10.1038/s41416-020-0822-x.Kawamura K., Komohara Y., Takaishi K., Katabuchi H., Takeya M. Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. Pathol Int. 2009; 59(5): 300–5. doi: 10.1111/j.1440-1827.2009.02369.x.Kawamura K., Komohara Y., Takaishi K., Katabuchi H., Takeya M. Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. Pathol Int. 2009; 59(5): 300–5. doi: 10.1111/j.1440-1827.2009.02369.x.Baci D., Bosi A., Gallazzi M., Rizzi M., Noonan D.M., Poggi A., Bruno A., Mortara L. The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors. Int J Mol Sci. 2020; 21(9): 3125. doi: 10.3390/ijms21093125.Baci D., Bosi A., Gallazzi M., Rizzi M., Noonan D.M., Poggi A., Bruno A., Mortara L. The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors. Int J Mol Sci. 2020; 21(9): 3125. doi: 10.3390/ijms21093125.Steitz A.M., Steffes A., Finkernagel F., Unger A., Sommerfeld L., Jansen J.M., Wagner U., Graumann J., Müller R., Reinartz S. Tumorassociated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (TGFBI) and tenascin C. Cell Death Dis. 2020; 11(4): 249. doi: 10.1038/s41419-020-2438-8.Steitz A.M., Steffes A., Finkernagel F., Unger A., Sommerfeld L., Jansen J.M., Wagner U., Graumann J., Müller R., Reinartz S. Tumorassociated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (TGFBI) and tenascin C. Cell Death Dis. 2020; 11(4): 249. doi: 10.1038/s41419-020-2438-8.Yin M., Li X., Tan S., Zhou H.J., Ji W., Bellone S., Xu X., Zhang H., Santin A.D., Lou G., Min W. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. J Clin Invest. 2016; 126(11): 4157–73. doi: 10.1172/JCI87252.Yin M., Li X., Tan S., Zhou H.J., Ji W., Bellone S., Xu X., Zhang H., Santin A.D., Lou G., Min W. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. J Clin Invest. 2016; 126(11): 4157–73. doi: 10.1172/JCI87252.Chandra A., Pius C., Nabeel M., Nair M., Vishwanatha J.K., Ahmad S., Basha R. Ovarian cancer: Current status and strategies for improving therapeutic outcomes. Cancer Med. 2019; 8(16): 7018–31. doi: 10.1002/cam4.2560.Chandra A., Pius C., Nabeel M., Nair M., Vishwanatha J.K., Ahmad S., Basha R. Ovarian cancer: Current status and strategies for improving therapeutic outcomes. Cancer Med. 2019; 8(16): 7018–31. doi: 10.1002/cam4.2560.Хохлова С.В. Новое в лечении high grade серозного рака яичников. Эффективная фармакотерапия. 2019; 15(38): 24–9. doi: 10.33978/23073586-2019-15-38-24-29.Khokhlova S.V. New in High Grade Serous Ovarian Cancer Treatment. Effective Pharmacotherapy. 2019; 15(38): 24–9. (in Russian). doi: 10.33978/23073586-2019-15-38-24-29.Högberg T., Glimelius B., Nygren P.; SBU-group. Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in ovarian cancer. Acta Oncol. 2001; 40(2–3): 340–60. doi: 10.1080/02841860151116420.Högberg T., Glimelius B., Nygren P.; SBU-group. Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in ovarian cancer. Acta Oncol. 2001; 40(2–3): 340–60. doi: 10.1080/02841860151116420.Sehouli J., Camara O., Schmidt M., Mahner S., Seipelt G., Otremba B., Schmalfeldt B., Tesch H., Lorenz-Schlüter C., Oskay-Ozcelik G.; North-Eastern German Society of Gynecological Oncology. Pegylated liposomal doxorubicin (CAELYX) in patients with advanced ovarian cancer: results of a German multicenter observational study. Cancer Chemother Pharmacol. 2009; 64(3): 585–91. doi: 10.1007/s00280-008-0909-1.Sehouli J., Camara O., Schmidt M., Mahner S., Seipelt G., Otremba B., Schmalfeldt B., Tesch H., Lorenz-Schlüter C., Oskay-Ozcelik G.; North-Eastern German Society of Gynecological Oncology. Pegylated liposomal doxorubicin (CAELYX) in patients with advanced ovarian cancer: results of a German multicenter observational study. Cancer Chemother Pharmacol. 2009; 64(3): 585–91. doi: 10.1007/s00280-008-0909-1.Zheng F., Zhang Y., Chen S., Weng X., Rao Y., Fang H. Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer. Biomed Pharmacother. 2020; 123. doi: 10.1016/j.biopha.2019.109661.Zheng F., Zhang Y., Chen S., Weng X., Rao Y., Fang H. Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer. Biomed Pharmacother. 2020; 123. doi: 10.1016/j.biopha.2019.109661.Pujade-Lauraine E., Ledermann J.A., Selle F., Gebski V., Penson R.T., Oza A.M., Korach J., Huzarski T., Poveda A., Pignata S., Friedlander M., Colombo N., Harter P., Fujiwara K., Ray-Coquard I., Banerjee S., Liu J., Lowe E.S., Bloomfield R., Pautier P.; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017; 18(9): 1274–84. doi: 10.1016/S1470-2045(17)30469-2. Erratum in: Lancet Oncol. 2017; 18(9): 510.Pujade-Lauraine E., Ledermann J.A., Selle F., Gebski V., Penson R.T., Oza A.M., Korach J., Huzarski T., Poveda A., Pignata S., Friedlander M., Colombo N., Harter P., Fujiwara K., Ray-Coquard I., Banerjee S., Liu J., Lowe E.S., Bloomfield R., Pautier P.; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017; 18(9): 1274–84. doi: 10.1016/S1470-2045(17)30469-2. Erratum in: Lancet Oncol. 2017; 18(9): 510.Farmer H., McCabe N., Lord C.J., Tutt A.N., Johnson D.A., Richardson T.B., Santarosa M., Dillon K.J., Hickson I., Knights C., Martin N.M., Jackson S.P., Smith G.C., Ashworth A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434(7035): 917–21. doi: 10.1038/nature03445.Farmer H., McCabe N., Lord C.J., Tutt A.N., Johnson D.A., Richardson T.B., Santarosa M., Dillon K.J., Hickson I., Knights C., Martin N.M., Jackson S.P., Smith G.C., Ashworth A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434(7035): 917–21. doi: 10.1038/nature03445.Pennington K.P., Walsh T., Harrell M.I., Lee M.K., Pennil C.C., Rendi M.H., Thornton A., Norquist B.M., Casadei S., Nord A.S., Agnew K.J., Pritchard C.C., Scroggins S., Garcia R.L., King M.C., Swisher E.M. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014; 20(3): 764–75. doi: 10.1158/10780432.CCR-13-2287.Pennington K.P., Walsh T., Harrell M.I., Lee M.K., Pennil C.C., Rendi M.H., Thornton A., Norquist B.M., Casadei S., Nord A.S., Agnew K.J., Pritchard C.C., Scroggins S., Garcia R.L., King M.C., Swisher E.M. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014; 20(3): 764–75. doi: 10.1158/10780432.CCR-13-2287.Hussein Y.R., Ducie J.A., Arnold A.G., Kauff N.D., Vargas-Alvarez H.A., Sala E., Levine D.A., Soslow R.A. Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes. Am J Surg Pathol. 2016; 40(3): 404–9. doi: 10.1097/PAS.0000000000000556.Hussein Y.R., Ducie J.A., Arnold A.G., Kauff N.D., Vargas-Alvarez H.A., Sala E., Levine D.A., Soslow R.A. Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes. Am J Surg Pathol. 2016; 40(3): 404–9. doi: 10.1097/PAS.0000000000000556.Pommier Y., O’Connor M.J., de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci Transl Med. 2016; 8(362). doi: 10.1126/scitranslmed.aaf9246. Erratum in: Sci Transl Med. 2016; 8(368).Pommier Y., O’Connor M.J., de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci Transl Med. 2016; 8(362). doi: 10.1126/scitranslmed.aaf9246. Erratum in: Sci Transl Med. 2016; 8(368).Paik J. Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Target Oncol. 2021; 16(6): 847–56. doi: 10.1007/s11523-021-00842-1.Paik J. Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Target Oncol. 2021; 16(6): 847–56. doi: 10.1007/s11523-021-00842-1.Monk B.J., Minion L.E., Coleman R.L. Anti-angiogenic agents in ovarian cancer: past, present, and future. Ann Oncol. 2016; 27(s1): 33–9. doi: 10.1093/annonc/mdw093.Monk B.J., Minion L.E., Coleman R.L. Anti-angiogenic agents in ovarian cancer: past, present, and future. Ann Oncol. 2016; 27(s1): 33–9. doi: 10.1093/annonc/mdw093.Sopo M., Anttila M., Hämäläinen K., Kivelä A., Ylä-Herttuala S., Kosma V.M., Keski-Nisula L., Sallinen H. Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer. BMC Cancer. 2019; 19(1): 584. doi: 10.1186/s12885-019-5757-3.Sopo M., Anttila M., Hämäläinen K., Kivelä A., Ylä-Herttuala S., Kosma V.M., Keski-Nisula L., Sallinen H. Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer. BMC Cancer. 2019; 19(1): 584. doi: 10.1186/s12885-019-5757-3.Orbegoso C., Marquina G., George A., Banerjee S. The role of Cediranib in ovarian cancer. Expert Opin Pharmacother. 2017; 18(15): 1637–48. doi: 10.1080/14656566.2017.1383384.Orbegoso C., Marquina G., George A., Banerjee S. The role of Cediranib in ovarian cancer. Expert Opin Pharmacother. 2017; 18(15): 1637–48. doi: 10.1080/14656566.2017.1383384.Hirte H., Lheureux S., Fleming G.F., Sugimoto A., Morgan R., Biagi J., Wang L., McGill S., Ivy S.P., Oza A.M. A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the Princess Margaret, Chicago and California Phase II Consortia. Gynecol Oncol. 2015; 138(1): 55–61. doi: 10.1016/j.ygyno.2015.04.009.Hirte H., Lheureux S., Fleming G.F., Sugimoto A., Morgan R., Biagi J., Wang L., McGill S., Ivy S.P., Oza A.M. A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the Princess Margaret, Chicago and California Phase II Consortia. Gynecol Oncol. 2015; 138(1): 55–61. doi: 10.1016/j.ygyno.2015.04.009.Ledermann J.A., Embleton-Thirsk A.C., Perren T.J., Jayson G.C., Rustin G.J.S., Kaye S.B., Hirte H., Oza A., Vaughan M., Friedlander M., González-Martín A., Deane E., Popoola B., Farrelly L., Swart A.M., Kaplan R.S., Parmar M.K.B.; ICON6 collaborators. Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial. ESMO Open. 2021; 6(2). doi: 10.1016/j.esmoop.2020.100043.Ledermann J.A., Embleton-Thirsk A.C., Perren T.J., Jayson G.C., Rustin G.J.S., Kaye S.B., Hirte H., Oza A., Vaughan M., Friedlander M., González-Martín A., Deane E., Popoola B., Farrelly L., Swart A.M., Kaplan R.S., Parmar M.K.B.; ICON6 collaborators. Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial. ESMO Open. 2021; 6(2). doi: 10.1016/j.esmoop.2020.100043.Brave S.R., Ratcliffe K., Wilson Z., James N.H., Ashton S., Wainwright A., Kendrew J., Dudley P., Broadbent N., Sproat G., Taylor S., Barnes C., Silva J.C., Farnsworth C.L., Hennequin L., Ogilvie D.J., Jürgensmeier J.M., Shibuya M., Wedge S.R., Barry S.T. Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family. Mol Cancer Ther. 2011; 10(5): 861–73. doi: 10.1158/1535-7163.MCT-10-0976.Brave S.R., Ratcliffe K., Wilson Z., James N.H., Ashton S., Wainwright A., Kendrew J., Dudley P., Broadbent N., Sproat G., Taylor S., Barnes C., Silva J.C., Farnsworth C.L., Hennequin L., Ogilvie D.J., Jürgensmeier J.M., Shibuya M., Wedge S.R., Barry S.T. Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family. Mol Cancer Ther. 2011; 10(5): 861–73. doi: 10.1158/1535-7163.MCT-10-0976.McCann K.E. Novel poly-ADP-ribose polymerase inhibitor combination strategies in ovarian cancer. Curr Opin Obstet Gynecol. 2018; 30(1): 7–16. doi: 10.1097/GCO.0000000000000428.McCann K.E. Novel poly-ADP-ribose polymerase inhibitor combination strategies in ovarian cancer. Curr Opin Obstet Gynecol. 2018; 30(1): 7–16. doi: 10.1097/GCO.0000000000000428.Lim J.J., Yang K., Taylor-Harding B., Wiedemeyer W.R., Buckanovich R.J. VEGFR3 inhibition chemosensitizes ovarian cancer stemlike cells through down-regulation of BRCA1 and BRCA2. Neoplasia. 2014; 16(4): 343–53. doi: 10.1016/j.neo.2014.04.003.Lim J.J., Yang K., Taylor-Harding B., Wiedemeyer W.R., Buckanovich R.J. VEGFR3 inhibition chemosensitizes ovarian cancer stemlike cells through down-regulation of BRCA1 and BRCA2. Neoplasia. 2014; 16(4): 343–53. doi: 10.1016/j.neo.2014.04.003.Bindra R.S., Crosby M.E., Glazer P.M. Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev. 2007; 26(2): 249–60. doi: 10.1007/s10555-007-9061-3.Bindra R.S., Crosby M.E., Glazer P.M. Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev. 2007; 26(2): 249–60. doi: 10.1007/s10555-007-9061-3.Chan N., Pires I.M., Bencokova Z., Coackley C., Luoto K.R., Bhogal N., Lakshman M., Gottipati P., Oliver F.J., Helleday T., Hammond E.M., Bristow R.G. Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment. Cancer Res. 2010; 70(20): 8045–54. doi: 10.1158/0008-5472.CAN-10-2352.Chan N., Pires I.M., Bencokova Z., Coackley C., Luoto K.R., Bhogal N., Lakshman M., Gottipati P., Oliver F.J., Helleday T., Hammond E.M., Bristow R.G. Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment. Cancer Res. 2010; 70(20): 8045–54. doi: 10.1158/0008-5472.CAN-10-2352.Qureshi O.S., Zheng Y., Nakamura K., Attridge K., Manzotti C., Schmidt E.M., Baker J., Jeffery L.E., Kaur S., Briggs Z., Hou T.Z., Futter C.E., Anderson G., Walker L.S., Sansom D.M. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011; 332(6029): 600–3. doi: 10.1126/science.1202947.Qureshi O.S., Zheng Y., Nakamura K., Attridge K., Manzotti C., Schmidt E.M., Baker J., Jeffery L.E., Kaur S., Briggs Z., Hou T.Z., Futter C.E., Anderson G., Walker L.S., Sansom D.M. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011; 332(6029): 600–3. doi: 10.1126/science.1202947.Daassi D., Mahoney K.M., Freeman G.J. The importance of exosomal PDL1 in tumour immune evasion. Nat Rev Immunol. 2020; 20(4): 209–15. doi: 10.1038/s41577-019-0264-y.Daassi D., Mahoney K.M., Freeman G.J. The importance of exosomal PDL1 in tumour immune evasion. Nat Rev Immunol. 2020; 20(4): 209–15. doi: 10.1038/s41577-019-0264-y.Salmaninejad A., Valilou S.F., Shabgah A.G., Aslani S., Alimardani M., Pasdar A., Sahebkar A. PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy. J Cell Physiol. 2019; 234(10): 16824–37. doi: 10.1002/jcp.28358.Salmaninejad A., Valilou S.F., Shabgah A.G., Aslani S., Alimardani M., Pasdar A., Sahebkar A. PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy. J Cell Physiol. 2019; 234(10): 16824–37. doi: 10.1002/jcp.28358.Yang C., Xia B.R., Zhang Z.C., Zhang Y.J., Lou G., Jin W.L. Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant. Front Immunol. 2020; 11. doi: 10.3389/fimmu.2020.577869.Yang C., Xia B.R., Zhang Z.C., Zhang Y.J., Lou G., Jin W.L. Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant. Front Immunol. 2020; 11. doi: 10.3389/fimmu.2020.577869.Gong J., Chehrazi-Raffle A., Reddi S., Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer. 2018; 6(1): 8. doi: 10.1186/s40425-018-0316-z.Gong J., Chehrazi-Raffle A., Reddi S., Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer. 2018; 6(1): 8. doi: 10.1186/s40425-018-0316-z.Keenan T.E., Burke K.P., Van Allen E.M. Genomic correlates of response to immune checkpoint blockade. Nat Med. 2019; 25(3): 389–402. doi: 10.1038/s41591-019-0382-x.Keenan T.E., Burke K.P., Van Allen E.M. Genomic correlates of response to immune checkpoint blockade. Nat Med. 2019; 25(3): 389–402. doi: 10.1038/s41591-019-0382-x.Conway J.R., Kofman E., Mo S.S., Elmarakeby H., Van Allen E. Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine. Genome Med. 2018; 10(1): 93. doi: 10.1186/s13073-018-0605-7.Conway J.R., Kofman E., Mo S.S., Elmarakeby H., Van Allen E. Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine. Genome Med. 2018; 10(1): 93. doi: 10.1186/s13073-018-0605-7.Pellegrino B., Musolino A., Llop-Guevara A., Serra V., De Silva P., Hlavata Z., Sangiolo D., Willard-Gallo K., Solinas C. Homologous Recombination Repair Deficiency and the Immune Response in Breast Cancer: A Literature Review. Transl Oncol. 2020; 13(2): 410–22. doi: 10.1016/j.tranon.2019.10.010.Pellegrino B., Musolino A., Llop-Guevara A., Serra V., De Silva P., Hlavata Z., Sangiolo D., Willard-Gallo K., Solinas C. Homologous Recombination Repair Deficiency and the Immune Response in Breast Cancer: A Literature Review. Transl Oncol. 2020; 13(2): 410–22. doi: 10.1016/j.tranon.2019.10.010.Paijens S.T., Vledder A., de Bruyn M., Nijman H.W. Tumorinfiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol. 2021; 18(4): 842–59. doi: 10.1038/s41423-020-00565-9.Paijens S.T., Vledder A., de Bruyn M., Nijman H.W. Tumorinfiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol. 2021; 18(4): 842–59. doi: 10.1038/s41423-020-00565-9.Plesca I., Tunger A., Müller L., Wehner R., Lai X., Grimm M.O., Rutella S., Bachmann M., Schmitz M. Characteristics of Tumor-Infiltrating Lymphocytes Prior to and During Immune Checkpoint Inhibitor Therapy. Front Immunol. 2020; 11: 364. doi: 10.3389/fimmu.2020.00364.Plesca I., Tunger A., Müller L., Wehner R., Lai X., Grimm M.O., Rutella S., Bachmann M., Schmitz M. Characteristics of Tumor-Infiltrating Lymphocytes Prior to and During Immune Checkpoint Inhibitor Therapy. Front Immunol. 2020; 11: 364. doi: 10.3389/fimmu.2020.00364.Andrikopoulou A., Zografos E., Apostolidou K., Kyriazoglou A., Papatheodoridi A.M., Kaparelou M., Koutsoukos K., Liontos M., Dimopoulos M.A., Zagouri F. Germline and somatic variants in ovarian carcinoma: A next-generation sequencing (NGS) analysis. Front Oncol. 2022; 12. doi: 10.3389/fonc.2022.1030786.Andrikopoulou A., Zografos E., Apostolidou K., Kyriazoglou A., Papatheodoridi A.M., Kaparelou M., Koutsoukos K., Liontos M., Dimopoulos M.A., Zagouri F. Germline and somatic variants in ovarian carcinoma: A next-generation sequencing (NGS) analysis. Front Oncol. 2022; 12. doi: 10.3389/fonc.2022.1030786.Тюляндина А.С., Коломиец Л.А., Морхов К.Ю., Нечушкина В.М., Покатаев И.А., Румянцев А.А., Тюляндин С.А., Урманчеева А.Ф., Хохлова С.В. Практические рекомендации по лекарственному лечению рака яичников, первичного рака брюшины и рака маточных труб. Злокачественные опухоли. 2022; 12(3s2-1): 198–211. doi: 10.18027/2224-5057-202212-3s2-198-211.Tyulyandina A.S., Kolomiets L.A., Morkhov K.Yu., Nechushkina V.M., Pokataev I.A., Rumyantsev A.A., Tyulyandin S.A., Urmancheeva A.F., Khokhlova S.V. Practical recommendations for the drug treatment of ovarian cancer, primary peritoneal cancer and fallopian tube cancer. Malignant Tumors. 2022; 12(3s2-1): 198–211. (in Russian)]. doi: 10.18027/2224-5057-202212-3s2-198-211.

The authors declare that there are no conflicts of interest present.