Scientists discuss in “Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization” new findings in angiogenesis. In this recently published article, scientists in the United States conducted a study “To test whether a direct antiangiogenic peptide (anginex) and a vascular endothelial growth factor antibody (bevacizumab, Avastin) can transiently normalize vasculature within tumors to improve oxygen delivery, alleviate hypoxia, and increase the effect of radiation therapy. Tumor oxygenation levels, microvessel density and pericyte coverage were monitored in three different solid tumor models (xenograft human ovarian carcinoma MA148, murine melanoma B16F10, and murine breast carcinoma SCK) in mice.”
“Multiple treatment schedules were tested in these models to assess the influence on the effect of radiation therapy. In all three tumor models, we found that tumor oxygenation levels, monitored daily in real time, were increased during the first 4 days of treatment with both anginex and bevacizumab. From treatment day 5 onward, tumor oxygenation in treated mice decreased significantly to below that in control mice. This “tumor oxygenation window” occurred in all three tumor models varying in origin and growth rate. Moreover, during the treatment period, tumor microvessel density decreased and pericyte coverage of vessels increased, supporting the idea of vessel normalization. We also found that the transient modulation of tumor physiology caused by either antiangiogenic therapy improved the effect of radiation treatment. Tumor growth delay was enhanced when single dose or fractionated radiotherapy was initiated within the tumor oxygenation window as compared with other treatment schedules. The results are of immediate translational importance because the clinical benefits of bevacizumab therapy might be increased by more precise treatment scheduling to ensure radiation is given during periods of peak radiosensitivity,” wrote R.P. Dings and colleagues, University of Minnesota, Department of Biochemistry.

The researchers concluded: “The oxygen elevation in tumors by non-growth factor-mediated peptide anginex suggests that vessel normalization might be a general phenomenon of agents directed at disrupting the tumor vasculature by a variety of mechanisms.”

Dings and colleagues published their study in Clinical Cancer Research (Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization. Clinical Cancer Research, 2007;13(11):3395-402).

For additional information, contact R.P. Dings, University of Minnesota, Dept. of Biochemistry, Minneapolis USA.

The publisher’s contact information for the journal Clinical Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.