Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities

Abstract

Ovarian cancer is the fifth most common cancer affecting women and at present, stands as the most lethal gynecologic malignancy. The poor disease outcome is due to the nonspecific symptoms and the lack of effective treatment at advanced stages. Thus, it is of utmost importance to understand ovarian carcinoma through several lenses and to dissect the role that the unique peritoneal tumor microenvironment plays in ovarian cancer progression and metastasis. This review seeks to highlight several determinants of this unique tumor microenvironment, their influence on disease outcome and ongoing clinical trials targeting these determinants.

Figure 1

Schematic representation of the key cell types in ovarian cancer microenvironment and the molecules involved in their interactions. HGSC, high‐grade serous cancer; LGSC, low‐grade serous cancer; CCC, clear cell carcinoma; EC, endometrial carcinoma; CIC, carcinoma in situ; CAA, cancer‐associated adipocyte; CAF, cancer‐associated fibroblast; FFA, free fatty acids; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; PDGF, platelet‐derived growth factor; VCAN, versican; CD8+, cytotoxic T cell; Treg, regulatory T cell; ECM, extracellular matrix; IL‐x, interleukin‐x; ICAM/VCAM, intercellular/vascular adhesion molecule; HA, hyaluronic acid; CA125, cancer antigen 125; LPA, lysophosphatidic acid; NK, natural killer cell; TAM, tumor‐associated macrophage; TGFβ, growth transforming growth factor β; TNFα, tumor necrosis factor‐α