Experimental modeling of ovarian carcinoma

Ya. Murazov, A. Nyuganen, A. Artem'yeva

N.N. Petrov National Medical Research Center of Oncology, Healthcare Ministry of Russia,

197758, Russia, St.-Petersburg, pos. Pesochniy, st. Leningradskaya 68

E-mail: yaroslav84@yandex.ru

Abstract

Despite the success achieved in the surgical and drug treatment of ovarian cancer, mortality among women from this malignant neoplasm remains high. Epithelial ovarian cancer (EOC) is the predominant histological type, and high-grade serous carcinoma (HGSC) is the main subtype of EOC, associated with approximately 90% of deaths. Currently, there is evidence of the dualistic origin of HGSC. Did it arise as a result of metaplastic transformation and simply morphologically resembled tumors of the oviduct (analogue of the fallopian tubes in women) or did it primarily arise from oviduct cells. Understanding the biology of tumor growth, assessing the efficacy and safety of pharmacological agents, new treatment methods (including normothermic, hyperthermic intraperitoneal chemotherapy), and studying prognostic and predictive biomarkers are impossible without reproducible experimental models in vivo that provide acceptable predictiveness of preclinical results for further clinical trials. The review presents data about the main groups of experimental models of EOC in laboratory animals. The advantages and disadvantages of spontaneous, carcinogen-induced, genetically engineered, syngeneic models are described. Transgenic models with inactivation of both p53 and Rb pathways, Brca 1/2, Pten, and Tp53 genes in the secretory epithelium of fallopian tubes (oviducts) of mice with double knockout of Dicer and Pten genes are described. Data on models based on transplantation of xenografts of human cell lines (A2780, OVCAR-3, and SKOV-3), as well as PDX (patient-derived xenograft) models in immunodeficient animals is presented. Anatomical sites of the main methods of xenograft transplantation (orthotopic and heterotopic) are considered. The morphological characteristics of the modeled malignant neoplasms are given. The metastatic potential of experimental models is described, information on the local and systemic dissemination of tumors, the formation of ascites is given. Our own results of studying high-grade syngeneic ovarian carcinoma in Wistar female rats are presented briefly. Applicable research areas are indicated for each model group. The article will be of interest to a wide range of specialists, involved in fundamental and registration preclinical studies.

Full text avaliable in Russain only

Acknowledgements

The study was performed without external funding.

Author’s сontributions

Murazov Y.G. – conception of the work, data collection and systematization, writing and editing of the manuscript

Niuganen A.O. –data collection and systematization, editing of the manuscript

Artemyeva A.S. – critical revision of the article, editing of the manuscript.

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