The mechanistic insights of the arrhythmogenic effect of trastuzumab

Biomed Pharmacother. 2021 Jul:139:111620. doi: 10.1016/j.biopha.2021.111620. Epub 2021 Apr 23.

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.

Keywords: Arrhythmia; Cardio-oncology; Cardiotoxicity; Electrophysiology; Trastuzumab.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Arrhythmias, Cardiac / chemically induced*
  • Cardiotoxicity / drug therapy
  • Humans
  • Myocardial Contraction / drug effects
  • Receptor, ErbB-2 / genetics
  • Trastuzumab / adverse effects*

Substances

  • Antineoplastic Agents
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab