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Using Angiogenesis Inhibitors Could Spell Danger
August 25, 2007 at 6:35 PM
Drug News
Several newly developed angiogenesis inhibitors work by blocking vascular endothelial growth factor (VEGF), an important signaling protein that spurs growth of new blood vessels. Avastin, an approved angiogenesis inhibitor for colon and lung cancers, inhibits angiogenesis by blocking VEGF signaling from outside of the cell.
UCLA researchers wanted to know what happened when VEGF signaling was blocked from within endothelial cells, a mechanism used by some small molecule drugs currently being tested in late phase clinical trials.
The result was unexpected, and sobering. More than half of the mice in the study suffered heart attacks and fatal strokes, while those that remained alive developed serious systemic vascular illness, said Luisa Iruela-Arispe, a professor of molecular, cell and developmental biology and director of the Cancer Cell Biology program at UCLAs Jonsson Cancer Center.
The study appears in Aug. 24, 2007 in the prestigious, peer-reviewed journal Cell. This was an extremely surprising result, said Iruela-Arispe, past president of the North American Vascular Biology Organization and a national expert on angiogenesis. I think this study is cause for some caution in the use of angiogenesis inhibitors in patients for very long periods of time and in particular for use of those inhibitors that block VEGF signaling from inside the cell.
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