Patient-Derived In Vitro Models of Ovarian Cancer: Powerful Tools to Explore the Biology of the Disease and Develop Personalized Treatments

SIMPLE SUMMARY: Ovarian cancer (OC) is a highly lethal neoplasm with a poor rate of response to current treatment. A prerequisite to designing and validating innovative and more efficacious therapies is a deeper understanding of the biological mechanisms that underlie OC progression and chemoresistance. Such an objective, in turn, requires experimental models that mimic the disease as faithfully as possible. In this context, great help comes from the use of patient-derived material, which is key to establishing clinically relevant models. This review summarizes the different categories of in vitro patient-derived OC models and outlines their ability to represent specific aspects of OC biology and provide new tools for personalizing the treatment of such a devastating disease. ABSTRACT: Epithelial ovarian cancer (OC) is the most lethal gynecological malignancy worldwide due to a late diagnosis caused by the lack of specific symptoms and rapid dissemination into the peritoneal cavity. The standard of care for OC treatment is surgical cytoreduction followed by platinum-based chemotherapy. While a response to this frontline treatment is common, most patients undergo relapse within 2 years and frequently develop a chemoresistant disease that has become unresponsive to standard treatments. Moreover, also due to the lack of actionable mutations, very few alternative therapeutic strategies have been designed as yet for the treatment of recurrent OC. This dismal clinical perspective raises the need for pre-clinical models that faithfully recapitulate the original disease and therefore offer suitable tools to design novel therapeutic approaches. In this regard, patient-derived models are endowed with high translational relevance, as they can better capture specific aspects of OC such as (i) the high inter- and intra-tumor heterogeneity, (ii) the role of cancer stem cells (a small subset of tumor cells endowed with tumor-initiating ability, which can sustain tumor spreading, recurrence and chemoresistance), and (iii) the involvement of the tumor microenvironment, which interacts with tumor cells and modulates their behavior. This review describes the different in vitro patient-derived models that have been developed in recent years in the field of OC research, focusing on their ability to recapitulate specific features of this disease. We also discuss the possibilities of leveraging such models as personalized platforms to design new therapeutic approaches and guide clinical decisions.