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Mechanisms of anthracycline-mediated cardiotoxicity and preventative strategies in women with breast cancer

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Abstract

While anthracyclines (ACs) are a class of chemotherapeutic agents that have improved the prognosis of many women with breast cancer, it is one of the most cardiotoxic agents used to treat cancer. Despite their reported dose-dependent cardiotoxicity, AC-based chemotherapy has become the mainstay of breast cancer therapy due to its efficacy. Elucidating the mechanisms of anthracycline-mediated cardiotoxicity and associated therapeutic interventions continue to be the main focus in the field of cardio-oncology. Herein, we summarized the current literature surrounding the mechanisms of anthracycline-induced cardiotoxicity, including the role of topoisomerase II inhibition, generation of reactive oxygen species, and elevations in free radicals. Furthermore, this review highlights the molecular mechanisms of potential cardioprotective interventions in this setting. The benefits of pharmaceuticals, including dexrazoxane, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, statins, and antioxidants in this setting, are reviewed. Finally, the mechanisms of emerging preventative interventions within this patient population including nutraceuticals and aerobic exercise are explored.

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Funding

This study was supported by Heart and Stroke Foundation of Canada and Molson’s Women Heart Health/ St. Boniface Foundation.

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  1. Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Sonu S. Varghese, Cameron R. Eekhoudt & Davinder S. Jassal

  2. Section of Cardiology, Department of Internal Medicine, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada

    Davinder S. Jassal

  3. Department of Radiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada

    Davinder S. Jassal

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  1. Sonu S. Varghese
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  2. Cameron R. Eekhoudt
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  3. Davinder S. Jassal
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Correspondence to Davinder S. Jassal.

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Varghese, S.S., Eekhoudt, C.R. & Jassal, D.S. Mechanisms of anthracycline-mediated cardiotoxicity and preventative strategies in women with breast cancer. Mol Cell Biochem 476, 3099–3109 (2021). https://doi.org/10.1007/s11010-021-04152-y

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