Inhibitors of Tumor Angiogenesis

Tumor-associated angiogenesis is one of the essential hallmarks underlying cancer development and metastasis. Antiangiogenic agents accordingly aim to restrain cancer progression by blocking the formation of new vessels, improving the delivery of chemotherapeutic agents to the tumor site, and reducing the shedding of metastatic cells into the circulation. The fact that the growth and spread of tumors are dependent on angiogenesis has led to the investigation of the role of antiangiogenic agents in the therapeutic strategies in several types of cancer. Benefits of the clinical use of direct or indirect inhibitors of tumor angiogenesis include an improvement of response rate and disease progression in many tumor types, but rarely improved overall survival. This may partly be due to patient selection, since various angiogenic factors contribute to the regulation of angiogenesis in the individual tumor, and induced resistance may occur through induction of compensatory pathways. In the era of personalized medicine, it is of importance to properly select patients who may benefit from a specific, potentially toxic, and expensive therapy. Due to the complex nature of tumor angiogenesis, various biomarkers or clinical markers are still only in the development phase. In this chapter, the current data from clinical studies are reported, and possible mechanisms of tumor resistance and predictive markers for antiangiogenic agents are summarized. © 2014 Elsevier Inc. All rights reserved.