Current Status of Patient-Derived Ovarian Cancer Models

Abstract

Ovarian cancer (OC) is one of the leading causes of female cancer death. Recent studies have documented its extensive variations as a disease entity, in terms of cell or tissue of origin, pre-cancerous lesions, common mutations, and therapeutic responses, leading to the notion that OC is a generic term referring to a whole range of different cancer subtypes. Despite such heterogeneity, OC treatment is stereotypic; aggressive surgery followed by conventional chemotherapy could result in chemo-resistant diseases. Whereas molecular-targeted therapies will become shortly available for a subset of OC, there still remain many patients without effective drugs, requiring development of groundbreaking therapeutic agents. In preclinical studies for drug discovery, cancer cell lines used to be the gold standard, but now this has declined due to frequent failure in predicting therapeutic responses in patients. In this regard, patient-derived cells and tumors are gaining more attention in precise and physiological modeling of in situ tumors, which could also pave the way to implementation of precision medicine. In this article, we comprehensively overviewed the current status of various platforms for patient-derived OC models. We highly appreciate the potentials of organoid culture in achieving high success rate and retaining tumor heterogeneity.

Keywords: drug discovery; organoid; ovarian cancer; patient-derived cells; pre-clinical model; precision medicine; spheroid; xenograft.

Figure 1

Representative approaches for establishing patient-derived cancer models from diverse clinical samples. Patient-derived xenografts (PDXs) are generated by direct engraftment of clinical samples into immunodeficient mice. Monolayer culture is a common culture method, but cells from primary tumors often undergo crisis, leading to positive selection of specific clones. Spheroid culture with serum-free media is suitable for enrichment of cancer stem-like cells. Cancer tissue-originated spheroids (CTOS) method initiates culture by maintaining cell-cell contact of cancer cells. In the presence of extracellular matrix (ECM) such as Matrigel, organoid culture can propagate both normal and cancer cells while retaining heterogeneity and differentiation. CTOS of ovarian cancer have been not documented yet. These cells cultured by various methods can be used to generate xenografts.