Cardio-oncology in targeting the HER receptor family: the puzzle of different cardiotoxicities of HER2 inhibitors.

Abstract

The HER family of tyrosine kinase receptors includes several members that are clinically important targets in cancer therapies, in particular HER1 (the EGF receptor) and HER2, other members include HER3 and HER4. Trastuzumab, a humanized monoclonal antibody and lapatinib, a tyrosine kinase inhibitor, are drugs that target HER2, which is highly expressed in 20-30% of breast cancers. Trastuzumab is recommended as an adjuvant therapy for lymph node positive, HER2-positive breast cancers, or node-negative cancer with high-risk of recurrence, as well as in stage IV cancers. One serious side effect of trastuzumab is cardiomyocyte dysfunction, resulting in reduced heart contractile efficiency. The incidence of collateral effects on the heart with trastuzumab therapy increases in people with cardiovascular risk factors, heart disease and when combined with other chemotherapeutics. When cardiotoxicity was observed with trastuzumab, several studies have addressed potential cardiac damage of trastuzumab itself and lapatinib. The differences in cardiovascular effects of these two compounds are somewhat unexpected and suggest distinct mechanisms of action, which have clear implications in clinical application and prevention of cardiotoxicity in cardio-oncological approaches.

• Authors: Adriana Albini, Eugenio Cesana, Francesco Donatelli, Rosaria Cammarota, Eraldo O Bucci, Massimo Baravelli, Claudio Anzà, Douglas M Noonan
• Journal: Future cardiology (Future Cardiol) Vol. 7 Issue 5 Pg. 693-704 (Sep 2011) ISSN: 1744-8298 [Electronic] England
• PMID: 21929348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Biomarkers, Tumor
• Protein Kinase Inhibitors
• Quinazolines
• Lapatinib
• Razoxane
• ERBB2 protein, human
• Protein-Tyrosine Kinases
• Receptor, ErbB-2
• Trastuzumab

Topics

• Antibodies, Monoclonal, Humanized (adverse effects, pharmacology, therapeutic use)
• Antineoplastic Agents (adverse effects, pharmacology, therapeutic use)
• Biomarkers, Tumor (blood)
• Breast Neoplasms (drug therapy)
• Female
• Gene Expression Regulation, Neoplastic
• Heart (drug effects)
• Humans
• Lapatinib
• Ovarian Neoplasms (drug therapy)
• Phosphorylation
• Protein Kinase Inhibitors (adverse effects, pharmacology)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Quinazolines (adverse effects, pharmacology)
• Razoxane (pharmacology)
• Receptor, ErbB-2 (adverse effects, antagonists & inhibitors, metabolism, pharmacology, therapeutic use)
• Signal Transduction (drug effects)
• Trastuzumab