Abstract
High-grade serous epithelial ovarian cancer (HGSC) is the most aggressive subtype of epithelial ovarian cancer. The identification of germline and somatic mutations along with genomic information unveiled by The Cancer Genome Atlas (TCGA) and other studies has laid the foundation for establishing preclinical models with high fidelity to the molecular features of HGSC. Notwithstanding such progress, the field of HGSC research still lacks a model that is both robust and widely accessible. In this review, we discuss the recent advancements and utility of HGSC genetically engineered mouse models (GEMMs) to date. Further analysis and critique on alternative approaches to modelling HGSC considers technological advancements in somatic gene editing and modelling prototypic organs, capable of tumorigenesis, on a chip.
Highlights
Epithelial ovarian cancer (OC) is the third most common gynaecologic cancer [1], with patients experiencing the worst prognosis and highest mortality rate of all gynaecological malignancies [2]
The most effort has undoubtedly gone into the development of genetically engineered mouse models (GEMMs) for the most common and aggressive subtype of OC, high-grade serous cancer (HGSC), which will be the main focus of this review
Tumour cell engraftment commonly occurs via intra-peritoneal (i.p.) injection in order to mimic the widespread metastatic disease seen in HGSC patients
Summary
Epithelial ovarian cancer (OC) is the third most common gynaecologic cancer [1], with patients experiencing the worst prognosis and highest mortality rate of all gynaecological malignancies [2]. These molecular phenotypes have been used to guide the development of genetically engineered mouse models (GEMMs) that attempt to recapitulate the initiation and development of OC. The most effort has undoubtedly gone into the development of GEMMs for the most common and aggressive subtype of OC, high-grade serous cancer (HGSC), which will be the main focus of this review. Most recent HGSC GEMMS: Pax8-rtTA; TetO-Cre; Brca1loxP/loxP; Trp53mut; PtenloxP/loxP [33] Ovgp1-iCreERT2; Brca1loxP/loxP; Trp53loxP/loxP; Rb1loxP/loxP; Nf1 loxP/loxP [34] Lgr5-Cre; Trp53R172H/+; T121 [35]
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