Novel Therapeutic Approaches Targeting Vascular Endothelial Growth Factor and its Receptors in Haematological Malignancies

The existence of specific angiogenesis inhibitors was first postulated by Judah Folkman in 1971. The term "antiangiogenesis" was introduced to describe treatments designed to prevent the induction of new blood vessels and perhaps reduce the number of those already present. Several approaches inhibit tumor angiogenesis and more than 60 antiangiogenic compounds have been clinically evaluated. Because tumorassociated angiogenesis takes place in a physiological context, its inhibition should not induce resistance and should potentiate the oncostatic effect, because each neovessel supplies hundreds of tumor cells. Inhibitors may be synthetic or semi-synthetic agents, endogenous inhibitors, or biological antagonists of the angiogenic cascade. Several direct and indirect vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitor strategies are under clinical investigation for treatment of solid tumors and hematological malignancies. Approaches to disrupt the VEGF/VEGFR signalling pathways range from small-molecule ATP competitive VEGFR inhibitors to biological agents such as soluble receptors, anti-VEGF and anti-VEGFR antibodies, small molecule inhibitors, and VEGF transcription inhibitors. This review summarizes the literature on the use of these molecules in the treatment of hematological malignancies.