Utility of Vascular Endothelial Growth Factor Inhibitors in the Treatment of Ovarian Cancer: From Concept to Application

Abstract

Despite recent advances in the management of ovarian cancer, it remains the most lethal gynecologic malignancy. Vascular endothelial growth factor (VEGF) has been shown to play a pivotal role in the progression of ovarian cancer leading to the eventual development of malignant ascites. On this basis, agents rendering VEGF ineffective by neutralizing VEGF (bevacizumab), blocking its receptors (aflibercept), or interfering with the postreceptor signaling pathways (sunitinib) provide us with the rational treatment options. These agents are generally used in combination with the standard chemotherapeutic drugs. Here, we discuss the basis of and the logic behind the use of these agents in the treatment of epithelial ovarian cancer, as well as their evaluation in different preclinical and clinical studies.

Discovery and Development of Antiangiogenetic Drugs in Ovarian Cancer

“…Major mechanisms of resistance include: redundant receptor signaling that results in the up-regulation of alternative pro-angiogenic pathways, epigenetic mechanisms of resistance, and tumor cell metastases to normal tissues that can benefit from normal tissue vasculature rather than requiring neovascularization [7]. Many patients either do not respond to antiangiogenic therapy or show disease progression.…”

Current Approaches to Endometrial Cancer

“…www.futuremedicine.com HER-2-positive compared with only 1% of endometrioid cancers [58]. When assessing the significance of HER-2 as a prognostic factor for recurrence and death, multiple studies have shown it be an independent risk factor in women with uterine serous carcinoma [59,60].…”

“…Side effects of angiogenesis inhibitors are hypertension, proteinuria, bleeding and gastrointestinal perforation [59]. Besides these toxicities and complications, tumor resistance to anti-VEGF agents remains an important and controversial issue [60].…”

Vascular endothelial growth factor inhibitors: investigational therapies for the treatment of psoriasis

“…Applications under investigation in oncology include treatment of: metastatic colorectal cancer,63 lung adenocarcinoma,53 inoperable melanoma,64 metastatic urothelial tumors,65 ovarian cancer,66 and recurrent malignant glioma 67…”