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The Molecular Mechanisms of Cardiotoxicity Induced by HER2, VEGF, and Tyrosine Kinase Inhibitors: an Updated Review

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Abstract

Aim

In recent decades, there has been a revolutionary decrease in cancer-related mortality and an increase in survival due to the introduction of novel targeted drugs. Nevertheless, drugs targeting human epidermal growth factor receptor 2 (HER-2), angiogenesis, and other tyrosine kinases also come with unexpected cardiac side effects, including heart failure, hypertension, arterial thrombosis, and arrhythmias, and have mechanisms that are unlike those of classic chemotherapeutic agents. In addition, it is challenging to address some problems, as the existing guidelines need to be more specific, and further large-scale clinical trials and experimental studies are required to confirm the benefit of administering cardioprotective agents to patients treated with targeted therapies. Therefore, an improved understanding of cardiotoxicity becomes increasingly important to minimize the pernicious effects and maximize the beneficial effects of targeted agents.

Methods

“Cardiotoxicity”, “targeted drugs”, “HER2”, “trastuzumab”, “angiogenesis inhibitor”, “VEGF inhibitor” and “tyrosine kinase inhibitors” are used as keywords for article searches.

Results

In this article, we report several targeted therapies that induce cardiotoxicity and update knowledge of the clinical evidence, molecular mechanisms, and management measures.

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Data Availability

All data generated or used during the study are available in a repository or online in accordance with funder data retention policies (provide full citations that include url or DOIs).

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Acknowledgements

We are grateful to Dr. Chenfang Dong and Mr. Zhanyu Wang of the Department of Surgical Oncology (Breast Center) of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, for the advice on cancer therapy and the critical reading of the manuscript.

Funding

This work was supported by The Natural Science Foundation of Shandong Province (no. ZR2020MH016), The Project of Shandong Province Higher Educational Science and Technology Program (no. J18KA285), The Cardiovascular Multidisciplinary Integrated Thinking Research Fund Scientific Research Public Welfare Project (no. Z-2016-23-2001-31), Grants from the National Natural Science Foundation of China (81871231). Youth Innovation and Science and Technology Plan of Colleges and Universities in Shandong Province (2019KJK016).

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Authors and Affiliations

  1. Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266100, Shandong, China

    Qinchao Wu, Baochen Bai, Chao Tian, Daisong Li, Haichu Yu, Bingxue Song & Xianming Chu

  2. Department of Hematology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, Shandong, China

    Bing Li

  3. Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, No. 308 Ningxia Road, Qingdao, 266000, Shandong, China

    Bing Li

  4. The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, Shandong, China

    Xianming Chu

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  1. Qinchao Wu
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Contributions

Qinchao Wu collected materials, prepared the figures and tables, and wrote the paper. Baochen Bai, Chao Tian, and Daisong Li collected materials and prepared the tables. Bingxue Song and Haichu Yu collected materials and provided clinical ideas. Xianming Chu and Bing Li provided ideas and revised the paper. All authors reviewed and approved the final paper.

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Correspondence to Bing Li or Xianming Chu.

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Wu, Q., Bai, B., Tian, C. et al. The Molecular Mechanisms of Cardiotoxicity Induced by HER2, VEGF, and Tyrosine Kinase Inhibitors: an Updated Review. Cardiovasc Drugs Ther 36, 511–524 (2022). https://doi.org/10.1007/s10557-021-07181-3

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