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Trastuzumab-mediated cardiotoxicity: current understanding, challenges, and frontiers
Nishant Mohan1, Jiangsong Jiang1, Milos Dokmanovic1
1Division of Biotechnology Review and Research 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Antibody Therapeutics
|September 15, 2018
Summary
Trastuzumab (HER2) antibody can cause heart damage. This review explores mechanisms, including DNA topoisomerase IIB, and its impact on combination therapies for cancer patients.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Trastuzumab is a targeted therapy for HER2-positive cancers.
- Cardiotoxicity is a significant clinical challenge with Trastuzumab.
- Mechanisms underlying Trastuzumab-induced cardiotoxicity require further elucidation.
Purpose of the Study:
- To review current understanding of Trastuzumab-mediated cardiotoxicity.
- To discuss the role of DNA topoisomerase IIB in combination therapy cardiotoxicity.
- To explore Trastuzumab's potential impact on immune checkpoint inhibitor therapies.
Main Methods:
- Literature review of Trastuzumab cardiotoxicity.
- Analysis of shared molecular targets.
- Speculative analysis of Trastuzumab in novel therapeutic combinations.
Main Results:
- Trastuzumab targets HER2, but can induce cardiotoxicity.
- DNA topoisomerase IIB is implicated in cardiotoxicity from Trastuzumab and anthracyclines.
- Trastuzumab's role in immunotherapy cardiotoxicity is under investigation.
Conclusions:
- Understanding Trastuzumab cardiotoxicity is crucial for patient safety.
- DNA topoisomerase IIB represents a potential therapeutic target to mitigate cardiotoxicity.
- Further research is needed on Trastuzumab's cardiovascular effects in combination therapies.
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