Linked Life Data

14529382

Source:http://linkedlifedata.com/resource/pubmed/id/14529382

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-10-7
pubmed:abstractText
The Hsp90 molecular chaperone has emerged as one of the most exciting targets for cancer drug development. Hsp90 is overexpressed in many malignancies, very likely as a result of the stress that is induced both by the hostile cancer microenvironment and also by the mutation and abberant expression of oncoproteins. A particularly attractive feature of Hsp90 as a cancer drug target is that it is required for the conformational stability and function of a wide range of oncogenic 'client' proteins, including c-Raf-1, Cdk4, ErbB2, mutant p53, c-Met, Polo-1 and telomerase hTERT. Inhibition of Hsp90 should therefore block multiple mission critical oncogenic pathways in the cancer cell, leading to inhibition of all the hallmark traits of malignancy. This combinatorial blockade of oncogenic targets should give rise to board spectrum antitumour activity across multiple cancer types. The 'druggability' of Hsp90 was confirmed by the discovery that the natural products geldanamycin and radicicol, which have anticancer activity, exert their biological effects by inhibiting the essential ATPase activity associated with the N-terminal domain of the protein. The first-in-class Hsp90 inhibitor has entered clinical trial and provided proof of concept that Hsp90 can be inhibited and clinical benefit seen at non-toxic doses. Further development is underway and a related analogue 17DMAG also shows promise in preclinical models. In addition, novel Hsp90 inhibitors have been identified using methods such as high throughput screening and x-ray crystallography. The opportunities and challenges involved in translating the fast moving biology of Hsp90 into patient benefit is discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1568-0096
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
297-300
pubmed:dateRevised
2008-9-9
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Overview: translating Hsp90 biology into Hsp90 drugs.
pubmed:affiliation
Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey SM2 5NG UK. Paul.Workman@icr.ac.uk
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't