Harnessing ovarian cancer ascites for translational science: models, biomarkers, and therapeutics

Ovarian cancer is one of the most lethal gynecological malignancies and is often associated with fluid build-up in the peritoneal cavity, known as ascites. Nearly one-third of patients with ovarian cancer present with ascites at the time of initial diagnosis, and more frequently with recurrent ovarian cancer. Ascites is a uniquely valuable tool for research, as it is representative of both the tumor and its microenvironment. Ascites is composed of cells (single cells and multicellular aggregates) and acellular components that contribute to the development of peritoneal metastasis and chemoresistance. Ascites is an underutilized resource that provides an opportunity to improve our understanding of ovarian cancer biology, identify novel drug targets, assess drug responses, and identify diagnostic and/or prognostic biomarkers. This review summarizes the current understanding of ovarian cancer ascites with a focus on, (1) etiology, (2) cytopathological and molecular characterization, (3) the role its cellular and acellular components play in shaping the tumor microenvironment, and (4) its application in translational research for drug development (organoids and patient-derived ascites xenografts) and biomarker discovery. Lastly, options for the treatment of malignant ascites, along with future opportunities to use ascites as a translational research tool to improve our understanding of ovarian cancer biology and to develop new therapeutic strategies, are discussed.