Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles.

BACKGROUND

Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality in women worldwide. Despite various attempts to improve the diagnosis and therapy of ovarian cancer patients, the survival rate for these patients is still dismal, mainly because most of them are diagnosed at a late stage. Up to 90% of ovarian cancers arise from neoplastic transformation of ovarian surface epithelial cells, and are usually referred to as epithelial ovarian cancer (EOC). Unlike most human cancers, which are disseminated through blood-borne metastatic routes, EOC has traditionally been thought to be disseminated through direct migration of ovarian tumor cells to the peritoneal cavity and omentum via peritoneal fluid. It has recently been shown, however, that EOC can also be disseminated through blood-borne metastatic routes, challenging previous thoughts about ovarian cancer metastasis.

CONCLUSIONS

Here, we review our current understanding of the most updated cellular and molecular mechanisms underlying EOC metastasis and discuss in more detail two main metastatic routes of EOC, i.e., transcoelomic metastasis and hematogenous metastasis. The emerging concept of blood-borne EOC metastasis has led to exploration of the significance of circulating tumor cells (CTCs) as novel and non-invasive prognostic markers in this daunting cancer. We also evaluate the role of tumor stroma, including cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs), endothelial cells, adipocytes, dendritic cells and extracellular matrix (ECM) components in EOC growth and metastasis. Lastly, we discuss therapeutic approaches for targeting EOC. Unraveling the mechanisms underlying EOC metastasis will open up avenues to the design of new therapeutic options. For instance, understanding the molecular mechanisms involved in the hematogenous metastasis of EOC, the biology of CTCs, and the detailed mechanisms through which EOC cells take advantage of stromal cells may help to find new opportunities for targeting EOC metastasis.