Study finds blocking angiogenesis signaling from inside cell may lead to serious healt...( Angiogenesis inhibitors that block a...)

Angiogenesis inhibitors that block a tumors development of an independent blood supply have been touted as effective cancer fighters that result in fewer side effects than traditional chemotherapy. However, a new study by researchers at UCLAs Jonsson Cancer Center showed that one method of blocking blood supply development could result in serious and potentially deadly side effects.

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.

About 5 percent of patients taking Avastin develop blood clot-related side effects, Iruela-Arispe said. But because Avastin was approved only three years ago, it is unclear what side effects m
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