CLINICAL EVALUATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN PEDIATRIC SOLID TUMOURS

Angiogenesis is required for tumor growth and metastasis and, therefore, represents an exciting target for cancer treatment. Angiogenesis is a complex process that is tightly regulated by pro- and anti-angiogenic growth factors. Physiologic angiogenesis takes place during tissue growth and repair, during the female reproductive cycle, and during fetal development. Pathologic angiogenesis is characterized by either excessive (e.g., cancer) or inadequate (e.g., coronary artery disease) neovascularization. Angiogenesis occurs in a series of complex and interrelated steps that involve the release ofpro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF). VEGF regulates both vascular proliferation and permeability, and functions as an anti-apoptotic factor for newly formed blood vessels. The biological effects of VEGF are mediated by two receptors, VEGF-1 and VEGF-2, whose expression is largely limited to the vascular endothelium. VEGF is often expressed in tumors at substantially increased levels. It is expressed in response to hypoxia, oncogenes, and other cytokines, and its expression is associated with poor prognosis in several types of cancer. Several different strategies have been used to inhibit VEGF, including anti-VEGF monoclonal antibodies and agents that inhibit the VEGF receptor.