Premium
Topoisomerase 2β: A Promising Molecular Target for Primary Prevention of Anthracycline‐Induced Cardiotoxicity
Author(s) -
Vejpongsa P,
Yeh ETH
Publication year - 2014
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2013.201
Subject(s) - cardiotoxicity , anthracycline , pharmacology , medicine , topoisomerase , chemotherapy , biology , cancer , dna , biochemistry , breast cancer
Anthracyclines are powerful chemotherapy agents that are still widely used today. However, their clinical use is limited by the development of dose‐dependent cardiotoxicity. Recently, we showed that topoisomerase 2β (Top2β) is required for anthracycline to induce DNA double‐strand breaks and changes in the transcriptome, leading to mitochondrial dysfunction and generation of reactive oxygen species. Furthermore, deleting Top2β from cardiomyocytes prevented the development of anthracycline‐induced cardiotoxicity in mice. On the basis of this molecular insight, new strategies should be developed to prevent anthracycline‐induced cardiotoxicity. First, Top2α‐specific anthracyclines should be tested to determine whether they will spare the heart. Second, Top2β should be studied as a potential biomarker to predict risk of developing cardiotoxicity before anthracycline treatment. Third, inhibiting and deleting Top2β in the heart should also be tested as primary prevention strategies. We propose that Top2β is a promising molecular target that can be used to design interventions to prevent anthracycline‐induced cardiotoxicity. Clinical Pharmacology & Therapeutics (2013); 95 1, 45–52 advance online publication 13 November 2013. doi: 10.1038/clpt.2013.201