Understanding the mechanisms of action of antiangiogenic agents in metastatic colorectal cancer: A clinician's perspective

- Mechanisms of action of antiangiogenic agents in metastatic colorectal cancer are reviewed.
- Preclinical data and clinical evidence are examined for each agent.
- We highlight distinctions in biological mechanism between therapies.
- Future directions of targeted antiangiogenic agents are discussed.

Multiple clinical trials using bevacizumab, ziv-aflibercept, and regorafenib have recently demonstrated efficacy for patients with metastatic colorectal cancer. While the net clinical benefit of each of these therapies in the second-line and refractory disease setting appears to be similar, important distinctions exist between the agents at the pharmacodynamic, tumor microenvironment, and clinical levels. The purpose of this review is to survey the preclinical evidence regarding the mechanisms of action of these novel antiangiogenic agents and provide an overview of their respective clinical activity, while highlighting distinctions between therapies. Fundamental understanding of these distinctions may aid in clinical decisions and choice of antiangiogenic therapies.