Recent clinical studies have suggested that antiangiogenic therapy is most effective when delivered in combination with radiation or chemotherapy. However, evidence supporting combined therapies has been inconsistent. Dr. Rakesh K. Jain from the Steele Laboratory for Tumor Biology at Massachusetts General Hospital and Harvard Medical School led a study to investigate whether the timing of combined therapy impacts treatment effectiveness.
Mice implanted with gliomas were treated with radiation, with the antiangiogenic agent DC101, or with combinations of the two. DC101 blocks the action of VEGF, a protein that stimulates blood vessel formation and is found at very high levels in gliomas. Blood vessels in gliomas and many other tumors are abnormal and do not deliver oxygen to tumor cells as efficiently as normal blood vessels do in normal tissues. This is clinically significant because lack of oxygen, or hypoxia, can make a tumor resistant to radiation therapy.
The researchers found that antiangiogenic therapy passively pruned some of the immature blood vessels of tumors and actively recruited pericytes, cells that support a blood vessel, to temporarily stabilize the tumor vasculature. During this period of vascular normalization, tumor hypoxia was substantially decreased and the effect of radiation treatment was enhanced. These results demonstrate that antiangiogenic therapy not only reduces the density of blood vessels in a tumor but, fo
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Cell Press
20-Dec-2004