Document Detail


Targeting human telomerase in cancer therapy.
MedLine Citation:
PMID:  12678725     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Telomerase is a specialized RNA template-containing reverse transcriptase that mediates telomere repeat synthesis at chromosome ends. The maintenance of telomere length and integrity is essential for cell survival. Telomerase is active in most immortal and tumor cells, whereas the majority of normal human cells demonstrate no detectable activity and undergo telomere shortening. The identification of a possible role for telomerase in cellular aging and cancer has led to numerous studies designed to characterize this ribonucleoprotein enzyme. Inhibiting telomerase activity in immortal human cells reduces cellular proliferative capacity and can lead to cell death. Identifying mechanisms to specifically inhibit telomerase activity in malignant cells could thus be of great therapeutic value in the treatment of cancer. In this review, we summarize the current understanding of the mechanism of action of human telomerase. The biochemical characterization of telomerase is necessary for the design and evaluation of antitelomerase therapies. Different strategies are currently under investigation to design inhibitors that target the reverse transcriptase and RNA components of the telomerase complex. Recent advances in the design of these inhibitors and their properties are discussed.
Authors:
Sylvain Huard; Chantal Autexier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current medicinal chemistry. Anti-cancer agents     Volume:  2     ISSN:  1568-0118     ISO Abbreviation:  Curr Med Chem Anticancer Agents     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2003-04-07     Completed Date:  2003-06-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101123597     Medline TA:  Curr Med Chem Anticancer Agents     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  577-87     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Cell Biology, McGill University, and Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, The Sir Mortimer B. Davis Jewish General Hospital, 3755 Côte Ste. Catherine Road, Montréal, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / chemistry,  pharmacology*,  therapeutic use
Catalytic Domain / drug effects
Drug Design
Enzyme Inhibitors / chemistry,  pharmacology,  therapeutic use*
Humans
Neoplasms / drug therapy,  enzymology,  pathology
Oligonucleotides / chemistry,  pharmacology,  therapeutic use
Telomerase / antagonists & inhibitors*,  chemistry,  metabolism
Telomere / chemistry,  metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Oligonucleotides; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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