Abstract
Epithelial ovarian carcinoma is the most predominant type of ovarian carcinoma, the deadliest gynecologic malignancy. It is typically diagnosed late when the cancer has already metastasized. Transcoelomic metastasis is the most predominant mechanism of dissemination from epithelial ovarian carcinoma, although both hematogenously and lymphogenously spread metastases also occur. In this review, we describe molecular mechanisms known to regulate organ-specific metastasis from epithelial ovarian carcinoma. We begin by discussing the sites colonized by metastatic ovarian carcinoma and rank them in the order of prevalence. Next, we review the mechanisms regulating the transcoelomic metastasis. Within this chapter, we specifically focus on the mechanisms that were demonstrated to regulate peritoneal adhesion—one of the first steps in the transcoelomic metastatic cascade. Furthermore, we describe mechanisms of the transcoelomic metastasis known to regulate colonization of specific sites within the peritoneal cavity, including the omentum. Mechanisms underlying hematogenous and lymphogenous metastatic spread are less comprehensively studied in ovarian cancer, and we summarize mechanisms that were identified to date. Lastly, we discuss the outcomes of the clinical trials that attempted to target some of the mechanisms described in this review.
Highlights
Ovarian carcinoma is the fifth leading cause of death from female cancers [1] and comprises several malignancies of epithelial and non-epithelial origins
Transcoelomic metastases from ovarian cancer primarily seed the viscera of organs and tissues of the peritoneal cavity; metastasizing cells first attach to the mesothelial monolayer of intraperitoneal tissues and subsequently invade the extracellular matrix of the underlying stroma
Distant metastases were not the cause of death in this study, they did occur, even though all but one patient survived between one and seven months after insertion of the shunts. In another patient-based study that focused on investigating the outcomes of inferior vena cava filter placement in patients with epithelial ovarian, fallopian, and primary peritoneal cancer, the authors reported that patients who underwent this procedure had significantly lower survival and significantly higher incidence of deep vein thrombosis and distant metastasis [110], supporting the role of a hematogenous route in seeding distant metastases from Epithelial ovarian carcinoma (EOC)
Summary
Ovarian carcinoma is the fifth leading cause of death from female cancers [1] and comprises several malignancies of epithelial and non-epithelial origins. The majority of patients with EOC are first diagnosed when peritoneal metastases have already formed, because the disease at early stages (when the tumor is confined to the ovary) is nearly asymptomatic These patients are typically treated by surgery and neoadjuvant chemotherapy (NACT) consisting of a combination of a platinum drug and a taxane. Cachexia is strongly associated with worse prognosis [20,21,22] For these reasons, the mechanisms regulating peritoneal metastasis from EOC are studied most extensively with the aim of identifying ways of preventing re-colonization of mesothelial linings and blocking or retarding the growth of intraperitoneal lesions using novel targeted molecular therapies that could be applied either alone or in conjunction with conventional chemotherapies.
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