Doxorubicin-Induced Heart Failure
Doxorubicin is a potent chemotherapy drug used to treat many types of cancer, including leukemia, lymphoma, carcinoma, soft tissue sarcoma, and bladder, breast, lung, stomach and ovarian cancers. Unfortunately, drug-induced cardiomyopathy is a common side effect and can lead to heart failure in cancer patients, not only during treatment, but months or years later.
"We hope to identify some drug which only blocks the side effect of doxorubicin but preserves the therapeutic effect," said Yan Liu, Ph.D., a postdoctoral researcher working in Dr. Randall Peterson's lab at the Massachusetts General Hospital.
Dr. Liu developed a zebrafish model of doxorubicin-induced cardiomyopathy. The fish experience heart failure within two days of treatment with symptoms similar to those seen in humans, including fewer heart muscle cells, ventricular collapse, and ineffective heartbeats.
The researchers used the model to screen through thousands of potential drug compounds and identified two visnagin and diphenylurea that both improved cardiac function and reduced doxorubicin-induced cell death in the heart. Importantly, both compounds specifically protected heart tissue, but not tumor cells, from the toxic effects of doxorubicin. Both seem to act through the suppression of a particular signaling pathway, the c-Jun N-terminal kinase pathway, in the heart cells but not tumor cells.
Dr. Liu also reported pro
|Contact: Phyllis Edelman|
Genetics Society of America