Antiangiogenic therapy: a novel approach to overcome tumor hypoxia.

Hypoxia is a common phenomenon in solid tumors. Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors. The growth and metastasis of solid tumors rely on blood vessels. Antiangiogenic agents mainly target tumor blood vessels, and radiation therapy mainly targets tumor cells. Combination of antiangiogenic treatment and radiation exhibits synergistic effect, which improves the response of tumors to radiation therapy. The mechanisms of interaction between antiangiogenic agents and ionizing radiation are complex and involve interactions between tumor cells and tumor microenvironment, including tumor oxygenation, stroma, and vasculature. The original mechanism of antiangiogenesis is to induce ischemia and hypoxia in tumors, thereby, "starve" the tumors. However, recently, emerging data suggest that antiangiogenic agents could reduce the proportion of hypoxic cells through normalizing tumor vasculature, decreasing oxygen consumption, and other mechanisms. The use of antiangiogenic agents provides a new approach to overcome the hypoxia problem, and ultimately improves the efficacy of radiation therapy. In this review, we discuss tumor hypoxia, tumor angiogenesis and its regulation, mechanisms of antiangiogenic therapy combined with radiation therapy, and how antiangiogenic therapy overcomes tumor hypoxia.