Document Detail


Cancer Therapy Targeting the HER2-PI3K Pathway: Potential Impact on the Heart.
MedLine Citation:
PMID:  22754526     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
The HER2-PI3K pathway is the one of the most mutated pathways in cancer. Several drugs targeting the major kinases of this pathway have been approved by the Food and Drug Administration and many are being tested in clinical trials for the treatment of various cancers. However, the HER2-PI3K pathway is also pivotal for maintaining the physiological function of the heart, especially in the presence of cardiac stress. Clinical studies have shown that in patients treated with doxorubicin concurrently with Trastuzumab, a monoclonal antibody that blocks the HER2 receptor, the New York Heart Association class III/IV heart failure was significantly increased compared to those who were treated with doxorubicin alone (16 vs. 3%). Studies in transgenic mice have also shown that other key kinases of this pathway, such as PI3Kα, PDK1, Akt, and mTOR, are important for protecting the heart from ischemia-reperfusion and aortic stenosis induced cardiac dysfunction. Studies, however, have also shown that inhibition of PI3Kγ improve cardiac function of a failing heart. In addition, results from transgenic mouse models are not always consistent with the outcome of the pharmacological inhibition of this pathway. Here, we will review these findings and discuss how we can address the cardiac side-effects caused by inhibition of this important pathway in both cancer and cardiac biology.
Authors:
Giannoula L Klement; David Goukassian; Lynn Hlatky; Joseph Carrozza; James P Morgan; Xinhua Yan
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Publication Detail:
Type:  Journal Article     Date:  2012-06-27
Journal Detail:
Title:  Frontiers in pharmacology     Volume:  3     ISSN:  1663-9812     ISO Abbreviation:  Front Pharmacol     Publication Date:  2012  
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-10-02     Revised Date:  2013-09-02    
Medline Journal Info:
Nlm Unique ID:  101548923     Medline TA:  Front Pharmacol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  113     Citation Subset:  -    
Affiliation:
Center of Cancer Systems Biology, St. Elizabeth's Medical Center, Tufts University School of Medicine Boston, MA, USA.
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Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
R01 GM093050/GM/NIGMS NIH HHS
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