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Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients

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Abstract

Breast cancer is the most frequently occurring cancer among women worldwide. Human epidermal growth factor receptor 2 (HER2 or ErbB2) is overexpressed in between 20 and 25% of invasive breast cancers and is associated with poor prognosis. Trastuzumab, an anti-ErbB2 monoclonal antibody, reduces cancer recurrence and mortality in HER2-positive breast cancer patients, but unexpectedly induces cardiac dysfunction, especially when used in combination with anthracycline-based chemotherapy. Novel approved ErbB2-targeting drugs, including lapatinib, pertuzumab, and trastuzumab-emtansine, also potentially cause cardiotoxicity, although early clinical studies demonstrate their cardiac safety profile. Unfortunately, the mechanism involved in causing the cardiotoxicity is still not completely understood. In addition, the use of preventive interventions against trastuzumab-induced cardiac dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, remain controversial. Thus, this review aims to summarize and discuss the evidence currently available from in vitro, in vivo, and clinical studies regarding the mechanism and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs.

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Acknowledgements

This work was supported by the Research Chair Grant from the National Science and Technology Development Agency Thailand (NC), the Thailand Research Fund RTA6080003 (SCC) and the Chiang Mai University Center of Excellence Award (NC).

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Krit Leemasawat & Arintaya Phrommintikul

  2. Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Arintaya Phrommintikul, Siriporn C. Chattipakorn & Nipon Chattipakorn

  3. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Nipon Chattipakorn

  4. Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand

    Arintaya Phrommintikul, Siriporn C. Chattipakorn & Nipon Chattipakorn

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  1. Krit Leemasawat
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  2. Arintaya Phrommintikul
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  3. Siriporn C. Chattipakorn
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  4. Nipon Chattipakorn
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Correspondence to Nipon Chattipakorn.

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Leemasawat, K., Phrommintikul, A., Chattipakorn, S.C. et al. Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients. Cell. Mol. Life Sci. 77, 1571–1589 (2020). https://doi.org/10.1007/s00018-019-03340-w

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  • DOI: https://doi.org/10.1007/s00018-019-03340-w

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