Moreover, anti-angiogenic therapy showed to produce a more invasive and aggressive tumor cell phenotype, including increased expression of other proangiogenic factors [51], upregulation of pro-invasion proteins such as matrix metalloproteinases[51], activation of proinvasive signaling pathway such as the phosphatidylinositol 3-kinase (PI3K)- and Wnt-signaling pathways [52]. The gene discussed is PROS1; the disease is neoplasm.