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Temple researchers show targeted cancer drug may stunt heart's ability to repair itself
Date:11/6/2012

he activity of a range of protein enzymes and specific targets in the cell that can contribute to the development and growth of cancer. In this case, sorafenib inhibits several RTKs, including c-kit, a receptor found on cardiac progenitor cells in heart and bone marrow, and can prevent the cardiac stem cell population from growing. Such progenitor and stem cell populations play important roles in cardiac repair.

Mortality Rates Following Induced Heart Attacks

The researchers wanted to see if they could better understand the mechanism behind these toxic effects. In the study, normal mice were given sorafenib for a week before being made to have the equivalent of a heart attack, and compared to mice that had a heart attack without receiving the drug. After one week, the mice that received sorafenib had significantly worse heart damage than the other group. Only 40 percent of those mice, versus 72 percent of the other group, were alive after one week. According to Dr. Houser, the doses were equivalent to those cancer patients would typically receive. Sorafenib by itself had no discernible effect on the mice prior to heart attack.

"Our study was to see if such a drug would put individuals with cancer and ischemic heart disease at extra risk for a heart attack," he said. "Mice given sorafenib and then made to have the equivalent of ischemic disease and a heart attack had much poorer heart function and survival. The drug put the animals at much greater risk for heart damage and death compared to animals without the drug."

Cancer patients tend to be middle-aged and older, and often have other significant health issues, including underlying heart disease. As a result, in patients with ischemic heart disease, there is already damage under repair. Drugs such as sorafenib may block or slow this repair process and increase the risk for a heart attack, Dr. Houser said.

Repair Process Inhibited

The researchers
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Contact: Steven Benowitz
steven.benowitz@tuhs.temple.edu
215-707-4784
Temple University Health System
Source:Eurekalert

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