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The mechanistic insights of the arrhythmogenic effect of trastuzumab
Natthaphat Siri-Angkul1, Siriporn C Chattipakorn2, Nipon Chattipakorn1
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Abstract:
Cardiovascular diseases and cancers are the leading causes of deaths globally, and an increasing proportion of cancer patients is suffering from cardiac adverse effects of chemotherapeutic drugs. Trastuzumab, a monoclonal antibody that inhibits the activity of the human epidermal growth factor receptor 2 (HER2), is a potent targeted therapy for HER2-positive malignancies. Despite the impressive antineoplastic efficacy, the cardiotoxicity of trastuzumab frequently limits its use. Trastuzumab-induced cardiac contractile dysfunction has been extensively studied, yet the electrophysiological side effect of trastuzumab remains poorly characterized. Growing evidence from basic and clinical studies supports the link between trastuzumab treatment and arrhythmias. This review comprehensively summarizes relevant information from those reports, discusses their limitations, and suggests future research directions. We aim to encourage further investigations that will provide valuable insights to devise cardioprotective strategies against trastuzumab-induced cardiotoxicity.
Insights
Trastuzumab, a cancer therapy, can cause heart rhythm problems (arrhythmias) by affecting heart cell electrical activity. Further research is needed to develop strategies protecting the heart from these side effects.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Cardiovascular diseases and cancers are leading global causes of death.
- Chemotherapy, including Trastuzumab, can cause cardiac adverse effects.
- Trastuzumab is a targeted therapy for HER2-positive cancers but carries cardiotoxicity risks.
Purpose of the Study:
- To review and summarize existing evidence on Trastuzumab-induced cardiotoxicity, focusing on electrophysiological effects.
- To discuss limitations in current research regarding Trastuzumab's cardiac side effects.
- To suggest future research directions for developing cardioprotective strategies.
Main Methods:
- Comprehensive literature review of basic and clinical studies.
- Analysis of existing data on Trastuzumab's impact on cardiac electrophysiology.
- Identification of knowledge gaps and research limitations.
Main Results:
- Trastuzumab treatment is increasingly linked to arrhythmias.
- While contractile dysfunction is well-studied, electrophysiological effects are less understood.
- Evidence suggests a significant association between Trastuzumab and cardiac rhythm disturbances.
Conclusions:
- Trastuzumab-induced cardiotoxicity, particularly arrhythmias, requires further investigation.
- Understanding electrophysiological mechanisms is crucial for managing Trastuzumab's cardiac risks.
- Future research should focus on devising effective cardioprotective strategies against Trastuzumab-induced cardiotoxicity.
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