Combining Angiogenesis Inhibitors with Radiation: Advances and Challenges in Cancer Treatment

Background: Radiation therapy is a widely employed modality that is used to destroy cancer cells, but it also tends to induce changes in the tumor microenvironment and promote angiogenesis. Radiation, when used as a sole means of therapeutic approach to treat cancer, tends to trigger the angiogenic pathways, leading to the upregulation of several angiogenic growth factors such as VEGF, bFGF, PDGF and angiogenin. This uncontrolled angiogenesis leads to certain angiogenic disorders like vascular outgrowth and an increase in tumor progression that can pose a serious threat to patients. Objective: This review emphasizes on various components of the tumor microenvironment, angiogenic growth factors and biological effects of radiation on tumors in provoking the relapse. It also describes the angiogenic mechanisms that trigger the tumor relapse after radiation therapy and how angiogenesis inhibitors can help in overcoming this phenomenon. It gives an overview of various angiogenesis inhibitors in pre-clinical as well as in clinical trials. Conclusion: The review focuses on the beneficial effects of the combinatorial therapeutic approach of anti-angiogenesis therapy and radiation in tumor management.