Antiangiogenic therapy for the treatment of pediatric solid malignancies

Although the past 30 years have seen remarkable progress in the treatment of childhood malignancies, not all types of cancer have enjoyed this improvement in prognosis. Because of this, clinical trials are ongoing in which novel treatment approaches are being evaluated, including immunotherapy, radionuclide therapy, and the use of agents that induce tumor apoptosis or differentiation. Additional treatment strategies are needed, however. One such strategy involves the use of angiogenesis inhibitors. Angiogenesis is the biologic process of new blood vessel formation. In addition to occurring as part of several normal, physiologic processes, angiogenesis is an essential component of a number of pathologic conditions, including cancer. Compelling data suggest that inhibition of angiogenesis can not only prevent tumor-associated neovascularization but also affect tumor growth and spread. An anticancer approach in which the tumor-induced new blood vessels are targeted is particularly appealing for several reasons. First, despite the extreme molecular and phenotypic heterogeneity of human cancer, it is likely that most, if not all, tumor types require neovascularization to achieve their full malignant phenotype. Therefore, antiangiogenic therapy may have broad applicability for the treatment of human cancer, as well as the many other pathologic processes that depend on angiogenesis. Second, the endothelial cells, although rapidly proliferating, are inherently normal with a very low rate of mutation. They are, therefore, unlikely to evolve an angiogenesis inhibitor-insensitive phenotype. This is in distinction to the rapidly proliferating tumor cells that do undergo a high rate of spontaneous mutation and therefore can readily generate drug-resistant clones. This review discusses progress in the development of antiangiogenic therapy for the treatment of pediatric solid tumors.