ABSTRACT
Within the gynecologic malignancies, angiogenic signaling has been most characterized in ovarian cancer. Cyclical changes in serum levels of vascular growth factors suggest that angiogenesis plays a key role in basic physiologic ovarian function (Kumaran et al. 2009). Current data suggest that angiogenesis plays a key role in metastatic spread, and increased angiogenic signaling is a poor prognostic factor in ovarian cancer (Hollingsworth et al. 1995; Abulafia et al. 1997; Alvarez et al. 1999; Goodheart et al. 2002; Gadducci et al. 2003; Rasila et al. 2005; Rubatt et al. 2009). Ovarian cancer cell lines and human tumors express higher levels of pro-angiogenic factors, such as hypoxia-inducible factor-1 (HIF-1), VEGF and PDGF as well as lower levels of anti-angiogenic factors, such as endostatins (Papetti and Herman 2002; Duhoux and Machiels 2010). The fundamental role of heightened angiogenesis in ovarian malignancy is supported by numerous clinical trials that have demonstrated efficacy of anti-angiogenic therapies in the upfront and recurrent clinical settings.
