Vascular endothelial growth factor as a target opportunity in hematological malignancies

Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with diverse biologic effects. There are seven members of the VEGF family, VEGF-A through VEGF-E, placental growth factor and the newly described, tissue-specific endocrine gland-derived VEGF. VEGF expression is induced by a number of stimuli including hypoxia, activated oncogenes, and inflammatory cytokines while negative regulators include wild type von Hippel-Lindau and p53 tumor suppressor genes. VEGF activity is mediated through interactions with high affinity tyrosine kinase receptors. To date, three have been identified. Interaction with these receptors activates multiple signal pathways leading to the diverse biologic activity of VEGF. Evidence suggests that VEGF is also a survival factor for endothelial cells and perhaps tumor cells. The importance of angiogenic factors such as VEGF, while clearly established in solid tumors, has not been fully elucidated in human hematopoietic neoplasms. Evolving data generally that elevated levels of VEGF confer a poor prognosis to patients with these diseases. The central role of VEGF in angiogenesis coupled with the relatively restricted expression of its receptors, has led to the development of a number of agents to target this system that are currently under clinical investigation.