Some anti-cancer drugs may not be suited for heart disease patients, researchers from Washington University School of Medicine, St. Louis have revealed.
The anticancer drugs, also known as hedgehog antagonists, interfere with a biochemical process that promotes growth in some cancer cells, however researchers have found that this interfering can further deteriorate of cardiac function.
"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," said senior author David Ornitz, M.D., Ph.D., the Alumni Endowed Professor and head of Developmental Biology.
Ornitz and his research team, including lead author Dr Kory Lavine, Ph.D., now a resident in the Cardiovascular Division of the Department of Medicine at Washington University School of Medicine had recently found that hedgehog signaling pathway was vital to heart's blood supply.
The new study showed that the hedgehog signaling process is important not just in the early development of the heart, but also in adult hearts for maintaining cardiac blood vessels.
The study conducted over mice showed that completely blocking hedgehog signaling in the hearts of adult mice caused many small coronary blood vessels to disappear, leaving heart muscle short of oxygen and leading to heart failure. I
In mice with induced heart attacks, mildly inhibiting hedgehog signaling led to a worsening of their heart conditions.
"We gave mice small amounts of antibodies against hedgehog, and in those that had a recent myocardial infarction (heart attack), this led to poorer heart function and some lethality," said Lavine.
"We've shown that small decreases in the hedgehog pathway in the setting of heart disease can lead to deleterious outcomes, and since a number of patients with cancer also have heart disease, this raises concern for those who might be treated with hedgehog antagonists," he added.
The researchers said that the role of hedgehog signaling in the vasculature of the heart means that it could be a target for new drugs that could be used to treat heart disease
The research was reported June 20, 2008, in advance online publication in the Journal of Clinical Investigation.