Journal
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume 13, Issue 7, Pages 755-766Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425255.2017.1337746
Keywords
ErbB2-targeted therapies; cardiotoxicity; trastuzumab; HER2/ErbB2-positive breast cancer; HER2/ErbB2-targeted therapy; drug development
Funding
- FDA-Office of Women's Health Research Science Program [750912CDR]
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Introduction: Trastuzumab, a therapeutic monoclonal antibody directed against ErbB2, is often noted as a successful example of targeted therapy. Trastuzumab improved outcomes for many patients with ErbB2-positive breast and gastric cancers, however, cardiac side effects [e.g., left ventricular dysfunction and congestive heart failure (CHF)] were reported in the early phase clinical studies. This finding, subsequently corroborated by multiple clinical studies, raised concerns that the observed cardiotoxicity induced by trastuzumab might adversely impact the clinical development of other therapeutics targeting ErbB family members. Areas covered: In this review we summarize both basic research and clinical findings regarding trastuzumab-induced cardiotoxicity and assess if there has been an impact of trastuzumab-induced cardiotoxicity on the development of other agents targeting ErbB family members. Expert opinion: There are a number of scientific gaps that are critically important to address for the continued success of HER2-targeted agents. These include: 1) elucidating the molecular mechanisms contributing to cardiotoxicity; 2) developing relevant preclinical testing systems for predicting cardiotoxicity; 3) developing clinical strategies to identify patients at risk of cardiotoxicity; and 4) enhancing management of clinical symptoms of cardiotoxicity.
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