Preclinical models of epithelial ovarian cancer: practical considerations and challenges for a meaningful application

Abstract

Despite many improvements in ovarian cancer diagnosis and treatment, until now, conventional chemotherapy and new biological drugs have not been shown to cure the disease, and the overall prognosis remains poor. Over 90% of ovarian malignancies are categorized as epithelial ovarian cancers (EOC), a collection of different types of neoplasms with distinctive disease biology, response to chemotherapy, and outcome. Advances in our understanding of the histopathology and molecular features of EOC subtypes, as well as the cellular origins of these cancers, have given a boost to the development of clinically relevant experimental models. The overall goal of this review is to provide a comprehensive description of the available preclinical investigational approaches aimed at better characterizing disease development and progression and at identifying new therapeutic strategies. Systems discussed comprise monolayer (2D) and three-dimensional (3D) cultures of established and primary cancer cell lines, organoids and patient-derived explants, animal models, including carcinogen-induced, syngeneic, genetically engineered mouse, xenografts, patient-derived xenografts (PDX), humanized PDX, and the zebrafish and the laying hen models. Recent advances in tumour-on-a-chip platforms are also detailed. The critical analysis of strengths and weaknesses of each experimental model will aid in identifying opportunities to optimize their translational value.

Keywords: GEMMs; Humanized mouse models; Organoids; Patient-derived EOC explants; Patient-derived EOC xenografts; Primary EOC cells.

Fig. 1

An overview of preclinical models of Epithelial Ovarian Cancer (EOC). PDE patient-derived explants, PDX patient-derived xenograft, humPDX humanized PDX, GEMMs genetically engineered mouse models. This figure was created with BioRender.com

Fig. 2

Distinctive features of in vitro preclinical models. Features are divided into model-favoring characteristics and limiting factors. PDE patient-derived explants, TME tumour microenvironment. This figure was created with BioRender.com

Fig. 3

Distinctive features of in vivo preclinical models. Features are divided into model-favoring characteristics and limiting factors. PDX patient-derived xenograft, humPDX humanized PDX, GEMMs genetically engineered mouse model, EPO-GEMM in vivo organ electroporation approach, TME tumour microenvironment. This figure was created with BioRender.com