Ovarian cancer is the most lethal gynecological
malignancy and the fifth most common cause of
cancer in women. It is characterized by diffuse
peritoneal carcinomatosis and often by large volumes of i.p.
ascites. Because
vascular endothelial growth factor (
VEGF), also known as
vascular permeability factor, increases vascular permeability and stimulates endothelial cell growth, its role in
ovarian cancer has been evaluated in a number of studies. However, questions remain regarding the ability of
VEGF alone to cause
ascites formation and the ability of
VEGF blockade to inhibit the growth of disseminated
cancer. We have used retroviral technology to create cell populations that overproduce
VEGF and report that enforced expression of
VEGF by ovarian
carcinoma cells dramatically reduces the time to onset of
ascites formation. In fact, even
tumor-free peritoneal overexpression of
VEGF, created by using adenoviral vectors, is sufficient to cause
ascites to accumulate. We have found that systemic administration of the
VEGF-Trap, a recently described high-affinity soluble decoy receptor for
VEGF, prevents
ascites accumulation and also inhibits the growth of disseminated
cancer. Remarkably, much as is observed in s.c.
tumor models,
VEGF blockade results in dramatic remodeling of the blood vessels in disseminated ovarian
carcinoma. The potent effects of the
VEGF-Trap in reducing both
ascites and
tumor burden suggest that it will be of value in a regimen for treatment of women with
ovarian cancer and
ascites.