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Study raises safety concerns about experimental cancer approach
Date:1/25/2011

A study by researchers at Washington University School of Medicine in St. Louis has raised safety concerns about an investigational approach to treating cancer.

The strategy takes aim at a key signaling pathway, called Notch, involved in forming new blood vessels that feed tumor growth. When researchers targeted the Notch1 signaling pathway in mice, the animals developed vascular tumors, primarily in the liver, which led to massive hemorrhages that caused their death.

Their findings are reported online Jan. 25 in the Journal of Clinical Investigation and will appear in the journal's February issue.

A number of anti-Notch therapies now are being evaluated in preclinical and early clinical trials for cancer. They target Notch1 as well as the three other signaling pathways in the Notch receptor family. The current research did not study any of these specific therapies in mice but instead focused on the potential side effects of chronically disrupting the Notch1 signal in individual cells.

"Our results suggest that anti-Notch1 strategies are bound to fail," says Raphael Kopan, PhD, professor of developmental biology and of medicine at the School of Medicine. "Without the Notch1 signal, cells in the vascular system grow uncontrollably and produce enlarged, weakened blood vessels. Eventually, the pressure within those vessels exceeds their capacity to hold blood, and they rupture, causing a dramatic loss of blood pressure, heart attack and death."

Notch plays a crucial role in determining a cell's fate and is active throughout a person's life. In recent years, the pathway has emerged as a target to block the formation of blood vessels called angiogenesis in solid tumors.

Kopan says he is not advising that anti-Notch clinical trials already under way be halted. These early trials generally involve short-term use of the drugs and are designed to assess safety. However, he says patients who take anti-Not
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Contact: Caroline Arbanas
arbanasc@wustl.edu
314-286-0109
Washington University School of Medicine
Source:Eurekalert  

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