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PMID: 15177193 Published · ppublish English Journal Article Review

Therapeutic and diagnostic implications of Hsp90 activation.

Trends in molecular medicine ·Vol. 10 ·No. 6 ·2004-06-00 ·Pages 283-90

Kamal A, Boehm MF, Burrows FJ

Abstract

The molecular chaperone heat-shock protein 90 (Hsp90) is involved in the stabilization and conformational maturation of many signaling proteins that are deregulated in cancers. Hsp90 inhibition results in the proteasomal degradation of these client proteins and leads to potent antitumor activity. The Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is presently in clinical trials. Recent work has identified the role of Hsp90 in multiple signal transduction pathways and revealed that the molecular mechanism of tumor selectivity by Hsp90 inhibitors is the result of an activated, high-affinity conformation of Hsp90 in tumors. This review discusses these recent advances in the understanding of tumor Hsp90 for the treatment and diagnosis of cancer. In addition, the role of Hsp90 in non-oncological diseases will also be discussed.

MeSH Terms
Animals Benzoquinones Clinical Trials as Topic Enzyme Activation/drug effects Enzyme Inhibitors/metabolism,therapeutic use HSP90 Heat-Shock Proteins/antagonists & inhibitors,metabolism Humans Lactams, Macrocyclic Neoplasms/diagnosis,drug therapy,metabolism,pathology Proteasome Endopeptidase Complex/metabolism Rifabutin/analogs & derivatives,metabolism,therapeutic use Signal Transduction/drug effects
Chemicals
Benzoquinones Enzyme Inhibitors HSP90 Heat-Shock Proteins Lactams, Macrocyclic Rifabutin tanespimycin Proteasome Endopeptidase Complex
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kamal Adeela
Department of Biology, Conforma Therapeutics Corporation, 9393 Towne Centre Drive, Suite 240, San Diego, CA 92121, USA. akamal@conformacorp.com
Boehm Marcus F
Burrows Francis J
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Article Info
Journal
Trends in molecular medicine
Abbr.
Trends Mol Med
ISSN
1471-4914
DOI
10.1016/j.molmed.2004.04.006
Email
akamal@conformacorp.com
Published
2004-06-00
Pages
283-90
Language
English
Region
England
NLM ID
100966035
PMCID
PMC7128344
Subset
IM
External Links
PubMed source DOI: 10.1016/j.molmed.2004.04.006 PMC Full Text View journal details
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