New anti-angiogenic strategies in pediatric solid malignancies: Agents and biomarkers of a near future

Importance of the field: Antiangiogenic strategies are affording considerable interest and have become a major milestone in therapeutics of various adult cancers. However, progress has been slow to expand such therapies to patients with pediatric solid malignancies. Areas covered in this review: This review discusses the principal pathways for angiogenesis in pediatric solid malignancies and summarizes recent preclinical and clinical data on antiangiogenesis strategies in these tumors. What the reader will gain: The reader will gain state-of-the-art knowledge in the current advancements of antiangiogenic therapies in pediatric clinical trials in regard to supporting preclinical data, and in the status of potential biomarkers investigated for monitoring angiogenesis inhibitors. Mechanisms of resistance to antiangiogenic therapy will also be discussed. Finally, we describe our experience in the monitoring of circulating endothelial cells and progenitors and their potential role as biomarkers of metastatic disease and resistance to antiangiogenic therapies. Take home message: Evaluation and development of antiangiogenesis protocols are starting and represent a crucial step in the management of pediatric solid malignancies today. Emphasis should be placed on the development of proper surrogate markers to monitor antiangiogenic activity and on the possible long-term effects of these therapies in a pediatric population.