Prevention of Heart Failure Induced by Doxorubicin with Early Administration of Dexrazoxane (PHOENIX Study): dose response and time course of dexrazoxane-induced degradation of topoisomerase 2b
- Published on 05/05/2025
- Reading time: 4 min.
Chang Hui-Ming 1,2,3, Hsu Jinn-Yuan 2, Ahn Chul 4, Yeh Edward T. H. 2,3
1 https://ror.org/00xcryt71 Department of Pharmacology and Toxicology University of Arkansas for Medical Sciences Little Rock AR USA
2 https://ror.org/00xcryt71 Department of Internal Medicine University of Arkansas for Medical Sciences Little Rock Arkansas USA
3 https://ror.org/00xcryt71 W. P. Rockefeller Cancer Institute University of Arkansas for Medical Sciences Little Rock Arkansas USA
4 https://ror.org/05byvp690 School of Public Health University of Texas Southwestern Medical Center Dallas TX USA
Abstract
Background Dexrazoxane, a putative iron chelator, is effective in preventing doxorubicin-induced cardiotoxicity. However, dexrazoxane is also a catalytic inhibitor of topoisomerase 2b (Top2b), a key mediator of doxorubicin toxicity. Preclinical studies have shown that dexrazoxane induces Top2b degradation, and early administration (8 h before doxorubicin) can prevent doxorubicin-induced cardiotoxicity. In this study, we investigated the dose–response relationship...
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