Tumor growth and survival is completely dependant upon having an adequate blood supply. In fact, the sensitivity of a tumor's blood vessels to radiation therapy is a major determinant of how successful the treatment will be. Recent studies have shown, however, that tumors can respond to radiation by secreting factors that promote the survival of blood vessel cells. Dr. Mark W. Dewhirst and colleagues from Duke University Medical Center have investigated the activation of this protective response and whether the process can be successfully inhibited, thereby maximizing the effectiveness of radiation therapy. The investigators focused on a molecule called hypoxia inducible factor-1 (HIF-1) that is known to stimulate the production of factors called cytokines that are related to tumor metabolism, growth, and blood vessel formation.
They found that HIF-1 levels were increased in tumors after radiation treatment, and that HIF-1-regulated cytokines decreased the sensitivity of blood vessels to radiation. Based on this knowledge, the investigators demonstrated that administration of low doses of a HIF-1 inhibitor in tumor-bearing mice dramatically enhanced the effectiveness of radiation therapy by destroying tumor blood vessels without having an impact on normal vessels.
These results indicate that HIF-1 acts as a major factor directing resistance of tumor vasculature to radiation therapy. According to Dr. Dewhirst, "We believe that by understanding how this protective response is activated, we can discover an effective means of inhibiting it.
This work takes a major step toward achieving t
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
17-May-2004