Antiangiogenic drugs as chemosensitizers in hematological tumors

Angiogenesis, the formation of new capillaries from preexisting blood vessels, plays an important role in cancer progression. When the tumor mass expands, the balance is shifted toward a pro-angiogenic milieu to maintain sustainable angiogenic processes. In this context, there is an up-regulation of several pro-angiogenic factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), placental growth factor (PlGF), platelet derived endothelial cell growth factor (PD-ECGF), angiopoietins (Angs), transforming growth factors (TGFs) -α and -β, and epidermal cell growth factor (EGF), which collectively activate the proliferation of circulating endothelial progenitor cells (EPCs) able to enter in the peripheral blood circulation, migrating to sites of angiogenesis. Hence, the number of antiangiogenic agents developed for cancer treatment has risen over the past years. To date, the most common approaches to the inhibition of the VEGF axis include the blockade of VEGF receptors (VEGFRs) or ligands by neutralizing antibodies, as well as the tyrosine kinase inhibitors (TKIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs). Here, we focus on the role of circulating EPCs, which mediate the cross-talk between cancer angiogenesis and neoplastic clone, as potential novel targets for antiangiogenic drugs with particular relevance for hematological malignancies.