Molecular mechanisms of cardiotoxicity induced by ErbB receptor inhibitor cancer therapeutics

Related Experiment Video

Updated: May 16, 2026

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
08:09

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

Anne-Sophie Hervent1, Gilles W De Keulenaer

  • 1Laboratory of Physiopharmacology (Building T2), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. gilles.dekeulenaer@ua.ac.be.

International Journal of Molecular Sciences
|December 4, 2012
PubMed

Insights

Targeted cancer therapies, like tyrosine kinase inhibitors, improve survival but can cause heart failure. Understanding ErbB receptor signaling and inhibitor cardiotoxicity is crucial for safer cancer treatments.

Area of Science:

  • Oncology
  • Cardiology
  • Pharmacology

Background:

  • Targeted therapies, particularly tyrosine kinase inhibitors, have advanced cancer treatment.
  • Despite improved survival, these therapies can cause significant cardiotoxicity, including left ventricular dysfunction and heart failure.
  • ErbB receptor tyrosine kinases are key targets in cancer therapy due to their roles in cancer development and normal physiology.

Purpose of the Study:

  • To review the rationale for targeting ErbB receptors in cancer therapy.
  • To discuss agents inhibiting the ErbB pathway.
  • To examine the mechanisms of cardiotoxicity associated with ErbB inhibitors.

Main Methods:

  • Literature review focusing on ErbB signaling in cancer and cardiac cells.
  • Analysis of ErbB receptor activation structures.
  • Examination of on-target and off-target cardiotoxicity mechanisms.

Main Results:

  • ErbB receptors, including EGFR and ErbB2, are critical in cancer development.
  • ErbB signaling plays a role in normal cardiac physiology.
  • Cardiotoxicity from ErbB inhibitors can be on-target or off-target.

Conclusions:

  • Targeting ErbB receptors offers a promising strategy for cancer treatment.
  • Understanding ErbB signaling in the heart is essential to mitigate cardiotoxicity.
  • Elucidating cardiotoxicity mechanisms can guide the development of safer anticancer drugs.

More Related Videos

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo05:14

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation08:03

Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation

Published on: October 20, 2022

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: