PGF and neoplasm: These treatment failures may be explained as follows [16, 19]: (i) some breast cancers are highly angiogenic and express low levels of VEGF; (ii) numerous proangiogenic growth factors such as PLGF, PDGFBB, and bFGF are present and can be up-regulated to drive angiogenesis when the VEGF pathway is inhibited [10]; and (iii) antiangiogenic therapy can increase tumor hypoxia, which induces an increase in HIF-1α expression to levels sufficient to activate genes that encode proteins required for the growth, invasion, and metastasis.