Tumor angiogenesis, the recruitment of new blood vessels, is essential for tumor growth and metastasis, and is driven by a balance between anti-angiogenic and pro-angiogenic factors . Anti-angiogenic therapy is emerging as an effective treatment for various tumor types through direct targeting of VEGF (such as the antibody bevacizumab) or the inhibition of VEGFRs by multi-target tyrosine kinase inhibitors (TKIs) [16–18]. These anti-angiogenesis strategies interfere with either the development or functionality of the tumor-associated vasculature, and thereafter lead to suppression of oxygen and nutrition supply to cancer cells . Recently, two different concepts have proposed that anti-angiogenic tumor therapy may either ‘‘normalize’’ dysfunctional tumor vasculature, which therefore facilitates drug delivery, or prevent recruitment of circulating endothelial precursors into the tumor [18, 19]. Although the outcomes of some clinical studies support either of these hypotheses, to date anti-angiogenesis therapy has yielded only modest therapeutic gains. The accurate mechanisms remain to a large extent unknown and the lack of an optimized mode of application limits the utility of this approach.