Modeling Platinum Sensitive and Resistant High-Grade Serous Ovarian Cancer: Development and Applications of Experimental Systems

Abstract

High-grade serous ovarian cancer remains the most common sub-type of ovarian cancer and, characterized by high degrees of genomic instability and heterogeneity, is typified by a transition from early response to acquired resistance to platinum-based chemotherapy. Conventional models for the study of ovarian cancer have been largely limited to a set of relatively poorly characterized immortalized cell lines and recent studies have called into question the validity of some of these as reliable models. Here, we review new approaches and models systems that take into account advances in our understanding of ovarian cancer biology and advances in the technology available for their generation and study. We discuss primary cell models, 2D, 3D, and organotypic models, and “paired” sample approaches that capture the evolution of chemotherapy failure within single cases. We also overview new methods for non-invasive collection of representative tumor material from blood samples. Adoption of such methods and models will improve the quality and clinical relevance of ovarian cancer research.

Identification of stably expressed reference small non‐coding RNAs for microRNA quantification in high‐grade serous ovarian carcinoma tissues

“…Epithelial ovarian cancer is the fifth most common type of cancer in women and the leading cause of mortality for gynaecological neoplasms, with high‐grade serous carcinoma (HGS‐OvCa) being the most frequent and aggressive histological type . The high mortality rate of HGS‐OvCa is because of the intrinsic biology of the disease that remains largely undetected, leading to a delayed diagnosis of patients presenting disseminated metastatic disease and, consequently, a 5‐year survival rate of only 30% . Recent investigations report microRNAs (miRNAs) as important players in human carcinogenesis and aberrantly expressed in several cancers, including ovarian carcinoma tissues .…”

Editorial: Advances in Epithelial Ovarian Cancer: Model Systems, Microenvironmental Influences, Therapy, and Origins

“…Ahmed and Stenvers draw attention to ascites, an underutilized yet readily accessible source of primary cancer cells from EOC patients and provide a detailed review of its use as a clinically relevant model system ( 4 ). Different methods of isolation and culture of primary ovarian cancer tumor cells from ascites and other sources are reviewed by Cunnea and Stronach who also advocate for universal standardized protocols for improved reproducibility and interpretation of results between studies ( 5 ).…”

“…In conjunction with the development of new cell models is the move to three-dimensional (3D) culture conditions. 3D culture systems feature in several articles in this Research Topic indicating the enthusiasm for this culture type and recognition of the deficiencies of the monolayer systems ( 2 , 5 , 6 ). It is hoped that models with more physiologically relevant microenvironments will lead to increased clinical translation of findings.…”

“…Resistance to platinum therapy continues to be a major issue in HG-SOC ( 5 , 7 , 8 ). Cunnea and Stronach review the currently available immortalized cell lines in the context of sensitivity and resistance to platinum and highlight deficiencies in in vitro development of treatment resistance ( 5 ).…”

“…Resistance to platinum therapy continues to be a major issue in HG-SOC ( 5 , 7 , 8 ). Cunnea and Stronach review the currently available immortalized cell lines in the context of sensitivity and resistance to platinum and highlight deficiencies in in vitro development of treatment resistance ( 5 ). In particular, they illustrate the power of having serial cell lines from the same patient which have been able to show that the development of treatment resistance was due to the selection of resistant sub-clones rather than evolution of new lineages.…”