Abstract
Simple SummaryAccumulation of excess fluid in the abdomen typically indicates abnormal function or disease, such as cancer, in the underlying tissues. This accumulation of fluid, or ascites, occurs more frequently in patients with advanced-stage ovarian cancer than any other type of cancer. The presence of ascites indicates the poorest outcomes for patients with advanced stage ovarian cancer, but little is known about the reasons for these dismal outcomes. This review discusses the current understanding of ascites, starting with an overview of ovarian cancer and ascites, followed by a description of the tools used to analyze the components of ascites and how these components modulate ovarian cancer biology. A perspective on the mechanical effects of ascites and the impact of mechanical stress on treatment resistance is provided. Lastly, treatment options for ascites and opportunities to develop new therapeutic strategies to improve outcomes are discussed.Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood. This review summarizes the current understanding of malignant ascites, with a focus on ovarian cancer. The first section provides an overview of heterogeneity in ovarian cancer and the pathophysiology of malignant ascites. Next, analytical methods used to characterize the cellular and acellular components of malignant ascites, as well the role of these components in modulating cell biology, are discussed. The review then provides a perspective on the pressures and forces that tumors are subjected to in the presence of malignant ascites and the impact of physical stress on therapy resistance. Treatment options for malignant ascites, including surgical, pharmacological and photochemical interventions are then discussed to highlight challenges and opportunities at the interface of drug discovery, device development and physical sciences in oncology.
Highlights
Compared to other gynecological malignancies, patients with ovarian cancer suffer from the highest mortality rates [1,2]
Transcoelomic metastases are frequently associated with the production of malignant ascites [1,20,36]. It is unclear whether transcoelomic metastases are a passive process, in which tumor cells that possess metastatic characteristics are transported to other intraperitoneal sites via peritoneal fluid, or an adaptive process in which cells undergo resistance to anoikis, epithelial to mesenchymal transition (EMT), and alterations in integrin expression [36]
In addition to being associated with type II tumors, ascites production and volume are correlated with advanced stage disease and increased metastatic spread [19,69]
Summary
Compared to other gynecological malignancies (cervical, uterine, vaginal, and vulva), patients with ovarian cancer suffer from the highest mortality rates [1,2]. Advanced-stage ovarian cancer is frequently associated with the accumulation of fluid in the abdomen, known as ascites, which is comprised of cellular and acellular components. Acellular factors in malignant ascites include cytokines, such as interleukin (IL)-6 IL8, proteins, and various metabolites [1,6] These cellular and acellular factors provide tumor cells with a growth-promoting and immune-evading microenvironment, enabling phenotypic changes within tumor cell populations and facilitating chemoresistance. Transcoelomic metastases are frequently associated with the production of malignant ascites [1,20,36] It is unclear whether transcoelomic metastases are a passive process, in which tumor cells that possess metastatic characteristics are transported to other intraperitoneal sites via peritoneal fluid, or an adaptive process in which cells undergo resistance to anoikis, epithelial to mesenchymal transition (EMT), and alterations in integrin expression [36]. Malignant ascites attenuates TRAIL-induced apoptosis and alters cytokine expression
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