Tumor Microvasculature as a Therapeutic Target During Radiotherapy

The controversy surrounding the use of antiangiogenic agents during radiotherapy is based upon the concern that the resulting hypoxia will impair tumor response to radiation (1). Tumor hypoxia is a therapeutic problem, as it makes solid tumors resistant to sparsely ionizing radiation and some forms of chemotherapy. Hypoxia also may increase the percentage of tumor cells in G1, resulting in greater resistance to therapy. Recent clinical studies suggest hypoxia can enhance malignant progression and increase aggressiveness through clonal selection and genome changes. In addition, hypoxia is an independent prognostic factor in cervix cancers, carcinomas of the head and neck, and soft-tissue sarcomas. Despite these concerns, recent preclinical studies have suggested that antiangiogenic agents enhance tumor control in response to fractionated irradiation.