Emerging and Evolving Ovarian Cancer Animal Models

Abstract

Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Xenograft studies in immunocompromised and immunocompetent mice have enhanced our knowledge of metastasis and immune cell involvement in cancer. Patient-derived xenografts (PDXs) can accurately reflect metastasis, response to therapy, and diverse genetics found in patients. Additionally, multiple genetically engineered mouse models have increased our understanding of possible tissues of origin for OC and what role individual mutations play in establishing ovarian tumors. Many of these models are used to test novel therapeutics. As no single model perfectly copies the human disease, we can use a variety of OC animal models in hypothesis testing that will lead to novel treatment options. The goal of this review is to provide an overview of the utility of different mouse models in the study of OC and their suitability for cancer research.

Keywords: Adeno-Cre; genetically engineered mouse models; high-grade serous ovarian cancer; ovarian cancer; patient-derived xenograft; xenograft.

Figure 1

Two-photon microscopy image of SKOV3IP tumor expressing green fluorescent protein (GFP). SKOV3IP labeled with GFP were injected SC into nude mice. After one week, two-photon microscopy was conducted to image tumor cells (green), collagen (blue), and vasculature (red). Therefore, imaging subcutaneous tumor can provide information about how genetic variation affects tumor microenvironment.

Figure 2

Tumor cells can be genetically manipulated in culture, and then implanted in mice to form a tumor. Growth of the tumor can be measured as well as response to chemotherapy. Genetic models of cancer have increased our understanding of how OC originates and what mutations or combinations of mutations may lead to tumor establishment by disruption of tumor suppressor genes, introduction of oncogenes, and tumor origin manipulations. These provide valuable information on metastasis and highlight potential therapeutic targets.