NIH R01 · 2024
Prevention of Heart Failure induced by Doxorubicin with Early Administration of Dexrazoxane
Doxorubicin, an inhibitor of DNA topoisomerase 2a (Top2a), is routinely used in the treatment of breast cancer, sarcoma, and pediatric leukemia. Of the two topoisomerase 2 isozymes, Top2a is highly expressed in cancer cells and is required for cell division. However, adult cardiomyocytes express only topoisomerase 2b (Top2b), which is involved in DNA transcription, but not DNA replication. Long-term cancer survivors who were treated with doxorubicin and other anthracyclines often suffer from dose-dependent cardiotoxicity. Laboratory data showed that Top2a mediates doxorubicin’s tumoricidal activity, whereas Top2b mediates doxorubicin’s cardiotoxic effect. At present, dexrazoxane is the only…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.