Document Detail


Hsp90, an unlikely ally in the war on cancer.
MedLine Citation:
PMID:  23356585     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
On the surface heat shock protein 90 (Hsp90) is an unlikely drug target for the treatment of any disease, let alone cancer. Hsp90 is highly conserved and ubiquitously expressed in all cells. There are two major isoforms α and β encoded by distinct genes and together they may constitute 1%-3% of the cellular protein. Deletion of the protein is embryonic lethal and there are no recognized polymorphisms suggesting an association or causal relationship with any human disease. With respect to cancer, the proteins absence from two recent high profile articles, 'Hallmarks of cancer: the next generation' [Hanahan & Weinberg (2011) Cell 144, 646-674] and 'Comprehensive molecular portraits of human breast tumours' [Koboldt et al. (2012) Nature] underlines the perception that it is an unlikely bona fide target to treat this disease. Yet, to date, there are 17 distinct Hsp90 inhibitors in clinical trials for multiple indications in cancer. The protein has been championed for over 20 years by the National Cancer Institute (Bethesda, MD, USA) as a cancer target since the discovery of the antitumor activity of the natural product geldanamycin. This review aims to look at the conundrum of why Hsp90 can even be considered a druggable target for the treatment of cancer. We propose that in contrast to the majority of chemotherapeutics our growing armamentarium of investigational Hsp90 drugs represents an elegant choice that offers real hope in the long-term treatment of certain cancers.
Authors:
Jared J Barrott; Timothy A J Haystead
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2013-02-24
Journal Detail:
Title:  The FEBS journal     Volume:  280     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-15     Completed Date:  2013-05-02     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  1381-96     Citation Subset:  IM    
Copyright Information:
© 2013 The Authors Journal compilation © 2013 FEBS.
Affiliation:
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal, Humanized / pharmacology
Antineoplastic Agents / pharmacology
Antineoplastic Combined Chemotherapy Protocols
Benzoquinones / pharmacology
Breast Neoplasms / drug therapy,  genetics,  metabolism*
Cell Cycle Proteins / genetics,  metabolism
Chaperonins / genetics,  metabolism
Clinical Trials as Topic
Female
Gene Expression Regulation, Neoplastic*
HSP90 Heat-Shock Proteins / antagonists & inhibitors,  genetics,  metabolism*
Humans
Lactams, Macrocyclic / pharmacology
Phosphorylation
Protein Folding
Protein Interaction Mapping
Grant Support
ID/Acronym/Agency:
1R01-AI089526-01/AI/NIAID NIH HHS; 1R01AI090644-01/AI/NIAID NIH HHS; R01 AI089526/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal, Humanized; 0/Antineoplastic Agents; 0/Benzoquinones; 0/CDC37 protein, human; 0/Cell Cycle Proteins; 0/HSP90 Heat-Shock Proteins; 0/Lactams, Macrocyclic; EC 3.6.1.-/Chaperonins; P188ANX8CK/trastuzumab; Z3K3VJ16KU/geldanamycin
Comments/Corrections

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