Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer

Abstract

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination.

A novel serum microRNA panel to discriminate benign from malignant ovarian disease

“…VEGF levels have been inversely correlated with survival. Furthermore, inhibition of VEGF found to suppress tumor invasion and metastasis [59].…”

Targeting JAK1/STAT3 Signaling Suppresses Tumor Progression and Metastasis in a Peritoneal Model of Human Ovarian Cancer

“…Peritoneal dissemination is the most common pathway for human ovarian cancer to metastasize (6,40). Although the role of STAT3 in promoting metastasis through the blood stream to remote sites has been reported for other solid tumors, including melanoma and breast cancer, the role of STAT3 in ovarian cancer peritoneal metastasis and ascites production was unknown (39,41-44).…”

“…Unfortunately, it is often not diagnosed until it has reached an advanced stage (1-3). Unlike other malignancies, ovarian cancer metastasizes less frequently to distant sites; it disseminates within the peritoneal cavity, and is associated with ascites formation (4-6). The extent of peritoneal carcinomatosis and ascites production are important prognostic factors for survival (5,7,8).…”

Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression

“…Of the complex mechanisms regulating blood vessel formation in cancer, the vascular endothelial growth factor (VEGF) family and associated receptors are recognized as a dominant pathway (2). VEGF (VEGF-A) exerts its effects largely through VEGF receptor (VEGFR)-2 and acts as the central promoter of tumor angiogenesis (3). As VEGF is constitutively overexpressed in many cancers, therapies targeting this pathway were highly anticipated additions to standard chemotherapeutic drugs (4).…”