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Study shows blood markers can help choose best dose for antiangiogenic drugs
Date:10/25/2007

Scientists at Sunnybrook have new information that may help to improve the use of anti-cancer drugs designed to block the growth of new blood vessels in tumors, a process called angiogenesis that is critical to tumor growth. While these antiangiogenic drugs are effective, at present there are no reliable methods for determining whether they are working, if the right dose is used, or if a patient will benefit (or not) from treatment.

A team led by Dr. Robert Kerbel - a senior scientist in Molecular and Cellular Biology at Sunnybrook and Canada Research Chair - has just published a paper in the October issue of the Proceedings of the National Academy of Sciences which may help to answer these questions. In the clinic, patients receiving these antiangiogenic drugs have a number of blood plasma proteins that rise and fall after treatment, so it is speculated that they could be used as surrogate biomarkers to tell us about drug activity and efficacy - our studies in mice show that this is correct, says Dr. Kerbel. In the study, Kerbels team found that drug-induced molecular changes observed in mice occurred at the same doses that had the best anti-tumor effect, suggesting that monitoring these changes in patients could predict the optimal dose of drug.

Surprisingly, the team also uncovered some unexpected insight into the nature of these observations. The current hypothesis to explain these drug-induced molecular changes is that they are tumor dependent, possibly because blocking blood flow would starve tumors of oxygen, which in turn would cause tumors to produce more proteins to recruit new vessels, says John Ebos, a doctoral student in Medical Biophysics at the University of Toronto and lead author of the study. However, our study shows that the same molecular changes occur in normal mice, that have no tumors, and come from multiple organs - suggesting that these changes come mainly from the body not the disease.

The study also found
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Contact: Natalie Chung-Sayers
natalie.chung-sayers@sunnybrook.ca
416-480-4040
Sunnybrook Health Sciences Centre
Source:Eurekalert

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