A set of promising new anticancer agents could have unforeseen risks in individuals with heart disease, suggests research at Washington University School of Medicine in St. Louis. The anticancer drugs which go by the strange name of hedgehog antagonists interfere with a biochemical process that promotes growth in some cancer cells. But the researchers showed that interfering with this biochemical process in mice with heart disease led to further deterioration of cardiac function and ultimately death.
"This finding should serve as a warning that these drugs might have adverse effects on the heart and that it could be very important to monitor patients' cardiovascular health when using this type of anticancer drug," says senior author David Ornitz, M.D., Ph.D., the Alumni Endowed Professor and head of Developmental Biology. The research was reported June 20, 2008, in advance online publication in the Journal of Clinical Investigation.
Hedgehog antagonists are drugs that inhibit the hedgehog signaling pathway, a chain of biochemical signals that regulate cellular growth and differentiation. The odd term hedgehog has little to do with the small, spiny mammals it originated when scientists noted the spiky, hedgehog-like appearance of fly embryos with abnormal hedgehog genes. Every organism in the animal kingdom has hedgehog genes, which play an essential role in guiding cells to mature into the appropriate form for proper function.
Ornitz and his research team, including lead author Kory Lavine, M.D., Ph.D., now a resident in the Cardiovascular Division of the Department of Medicine at Washington University School of Medicine, are on the forefront of research into how blood vessels in heart muscle develop in growing embryos. They recently found that the hedgehog signaling pathway was vital to the development of the heart's blood supply.
Now the Washington University research team has demonstrated that the hedgehog signal
|Contact: Gwen Ericson|
Washington University School of Medicine