The emerging role of anti-angiogenic therapy in ovarian cancer (review).

The introduction of new therapeutic agents into clinical practice of ovarian cancer, in addition to the role of surgery and chemotherapy, has been the subject of numerous studies because this tumor remains worldwide the most lethal gynecological cancer. It is now known that angiogenesis plays a vital role for ovarian physiology, but also in ovarian carcinogenesis and so it has become the main target of ovarian cancer treatment. In this review, the most common molecular pathways of angiogenesis have been investigated leading to the identification of novel targets, including monoclonal antibodies and tyrosine kinase inhibitors. The fundamental targets of anti-angiogenic drugs are vascular endothelial growth factor receptor and its ligand, but also platelet-derived growth factor, fibroblast growth factor and angiopoietin. Moreover, improved knowledge of angiogenic process allowed the discovery of other molecules, such as semaphorins, neuropilins, clusterin, some transcriptional factors, and the identification of features, including stemness, epithelial-mesenchymal transition, downregulation of certain microRNAs, the alteration of immune system, that contribute to angiogenesis and possibly to resistance mechanisms. The following patent and literature review aim to highlight recent findings of approved and novel anti-angiogenic drugs that make the treatment of patients with ovarian cancer a rapidly growing field of oncology.