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Mechanisms of Anthracycline Cardiotoxicity and Strategies to Decrease Cardiac Damage

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Abstract

Anthracyclines are common chemotherapeutic agents used to treat many different types of cancer. Unfortunately, the use of anthracyclines is limited by their cardiotoxic effects, which may become manifest as late as 20 years from initial exposure. Studies in cells and animals suggest that the mechanism of anthracycline-induced cardiotoxicity (AIC) is multifactorial. Anthracyclines induce multiple forms of cellular injury by free radical production. In addition, anthracyclines alter nucleic acid biology by intercalation into DNA and modulate intracellular signaling, leading to cell death and the disruption of homeostatic processes such as sarcomere maintenance. In an effort to decrease AIC, many strategies have been tested, but no specific therapies are universally acknowledged to prevent or treat anthracycline-induced cardiac dysfunction. Newer imaging modalities and cardiac biomarkers may be useful in improving early detection of cardiac injury and dysfunction. As long as there is no cardiac-specific therapy for AIC, evidence suggests that high-risk patients will benefit from prophylactic treatment with neurohormonal blockade by angiotensin-converting enzyme inhibitors and beta-adrenergic receptor blockers.

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Acknowledgments

Dr. Geisberg is supported by a fellowship from the Heart Failure Society of America. Dr. Sawyer is supported by an Established Investigator Award from the American Heart Association, as well as NIH R01 HL068144.

Disclosure

Dr. D. Sawyer has received payments (part of licensing fees paid by Zensun) related to his role as a coinventor of recombinant neuregulin for the treatment of heart failure. He is currently receiving grant support from Acorda Therapeutics related to the development of recombinant neuregulin. Dr. C. Geisberg reports no conflicts of interest.

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  1. Vanderbilt University, 2220 Pierce Avenue, 383 Preston Research Building, Nashville, TN, 37232-6300, USA

    Carrie Anna Geisberg & Douglas B. Sawyer

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  1. Carrie Anna Geisberg
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  2. Douglas B. Sawyer
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Correspondence to Carrie Anna Geisberg.

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Geisberg, C.A., Sawyer, D.B. Mechanisms of Anthracycline Cardiotoxicity and Strategies to Decrease Cardiac Damage. Curr Hypertens Rep 12, 404–410 (2010). https://doi.org/10.1007/s11906-010-0146-y

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