Getting to Know Ovarian Cancer Ascites: Opportunities for Targeted Therapy-Based Translational Research

Nuzhat Ahmed,Kaye L Stenvers

doi:10.3389/fonc.2013.00256

Abstract

More than one third of ovarian cancer patients present with ascites at diagnosis, and almost all have ascites at recurrence. The presence of ascites correlates with the peritoneal spread of ovarian cancer and is associated with poor disease prognosis. Malignant ascites acts as a reservoir of a complex mixture of soluble factors and cellular components which provide a pro-inflammatory and tumor-promoting microenvironment for the tumor cells. Subpopulations of these tumor cells exhibit cancer stem-like phenotypes, possess enhanced resistance to therapies and the capacity for distal metastatic spread and recurrent disease. Thus, ascites-derived malignant cells and the ascites microenvironment represent a major source of morbidity and mortality for ovarian cancer patients. This review focuses on recent advances in our understanding of the molecular, cellular, and functional characteristics of the cellular populations within ascites and discusses their contributions to ovarian cancer metastasis, chemoresistance, and recurrence. We highlight in particular recent translational findings which have used primary ascites-derived tumor cells as a tool to understand the pathogenesis of the disease, yielding new insights and targets for therapeutic manipulation.

Highlights

Ovarian cancer has the highest mortality rate of all gynecological cancers worldwide and is frequently (>75%) diagnosed at an advanced-stage [1]
More than one third of ovarian cancer patients present with malignant ascites at diagnosis; development of ascites is a fundamental part of chemoresistant and recurrent disease [2, 3]
The accessibility of ascites undeniably provides a rich source of tumor samples to monitor the course of chemotherapy treatment in patients

Summary

INTRODUCTION

Ovarian cancer has the highest mortality rate of all gynecological cancers worldwide and is frequently (>75%) diagnosed at an advanced-stage [1]. The early steps of cancer progression involve disruption of the ovarian tumor capsules and shedding of malignant cells from the primary tumors into the peritoneum where they survive as single cells or free-floating multicellular aggregates, commonly known as spheroids, in the ascites. Under this scenario, attachment and disaggregation of spheroids on mesothelial extracellular matrix (ECM) allows them to anchor as secondary lesions on pelvic organs and at a later stage, metastasize to distant organs [9, 10].

Ahmed and Stenvers

Findings

CONCLUSION