COLUMBUS, Ohio - Blocking a protein in the heart that is produced under stressful conditions could be a strategy to prevent cardiac damage that results from chemotherapy, a new study suggests.
Previous research has suggested that up to a quarter of patients who receive the common chemotherapy drug doxorubicin are at risk of developing heart failure later in life. Exactly how that heart damage is done remains unclear.
In this study, scientists identified a protein called heat shock factor-1 (HSF-1) as a likely source of chemotherapy-related heart damage in mice and cell cultures. Heat shock factor-1 is known to be induced by stress - in this case, the chemotherapy treatment itself.
"We have found that a simple stress-related factor could be aggravating chemotherapy's effect on the heart," said Govindasamy Ilangovan, associate professor of internal medicine at Ohio State University and senior author of the study. "The results are leading us toward the idea that any additional stress could hurt the heart more than what chemotherapy itself can do."
The researchers gave doxorubicin to two sets of mice - normal animals and mice that were genetically altered so they could not produce HSF-1. Mice without HSF-1 had healthier hearts and lived longer after the chemotherapy treatment than did normal mice.
A closer examination on the cellular level suggested that when HSF-1 is blocked in the heart, this condition allows for the activation of a gene that produces a protein to pump the chemo medicine out of heart muscle cells, preventing these cells from dying.
Ilangovan and colleagues are working to design drugs that could selectively inhibit HSF-1 in the heart as a potential additional therapy for cancer patients undergoing chemo treatment.
The research appears this week in the Proceedings of the National Academy of Sciences Online Early Edition.
Chemotherapy targets cancer cells, but it also
|Contact: Govindasamy Ilangovan|
Ohio State University