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.

Both Fallopian Tube and Ovarian Surface Epithelium Can Act as Cell-of-Origin for High Grade Serous Ovarian Carcinoma

“…Although HGSOC usually arises from FTE, whether OSE can also give rise to HGSOC had been less clear. Studies in which oncogenic defects were induced by Ad-Cre injections into the ovarian bursa were interpreted as indicating an OSE cell-of-origin (56,57), although others have argued that such injections can result in infection of adjacent tissue, including the oviduct or even the uterus (58). Indeed, our lineage tracing experiments show clearly that bursal injection can target FTE as well as OSE.…”

Marine Collagen Substrates for 2D and 3D Ovarian Cancer Cell Systems

“…Low success rates in OvCa specific drug discovery are linked, in part, to the lack of advanced preclinical in vitro screening methods (Ocana et al, 2010;Hutchinson and Kirk, 2011). Many mouse models have been used to interrogate the complexities of ovarian cancer, with orthotopic and humanized mouse models aiding the understanding of ovarian tumorigenesis and immunotherapy (Fong and Kakar, 2009;Bobbs et al, 2015;Hasan et al, 2015). Animal models can mimic some, but not all, of the important facets of human responses.…”

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

“…Many animal models include the use of immune incompetent mice; however, in the light of recent drug discoveries; we know that the immune system is a key player influencing therapy mechanisms and nowadays a target of therapy itself. Therefore, such a notion should not be generally excluded in therapy assays (41).…”