Document Detail


Telomere maintenance as therapeutic target in embryonal tumours.
MedLine Citation:
PMID:  20017721     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Embryonal tumours most commonly occur in the first few years of life and account for approximately 30% of childhood malignancies. Knowledge of these tumours' genetics has already impacted on their clinical management and further knowledge of their cellular immortalization will hopefully result in novel therapies. The ends of human chromosomes are capped and protected by telomeres; cellular replication, however, causes their loss. A critical length of telomere repeats is required to ensure proper telomere function and avoid the activation of DNA damage pathways that result in senescence and cell death. To proliferate beyond the senescence checkpoint, cells must restore their telomere length. Hence stabilization of telomere is an important step in cell immortalization and carcinogenesis. Telomere maintenance is evident in virtually all types of malignant cells, including embryonal tumours, where either a telomerase-dependent or alternative lengthening of telomeres (ALT) mechanism is employed in order to ensure their limitless replicative potential. For this reason effective strategies targeting telomere maintenance in cancer cells require a combination of telomerase and ALT inhibitors. In this review, we are giving an overview about telomere maintenance in childhood tumours and discussing its potential as a new therapeutic target.
Authors:
T Shalaby; E Hiyama; M A Grotzer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Anti-cancer agents in medicinal chemistry     Volume:  10     ISSN:  1875-5992     ISO Abbreviation:  Anticancer Agents Med Chem     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-04-22     Completed Date:  2010-07-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265649     Medline TA:  Anticancer Agents Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  196-212     Citation Subset:  IM    
Affiliation:
Neuro-Oncology Program, Department of Oncology, University Children's Hospital of Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / therapeutic use*
Child
Embryo, Mammalian / enzymology
G-Quadruplexes / drug effects
Hepatoblastoma / genetics
Humans
Medulloblastoma / genetics
Mice
Neoplasms, Germ Cell and Embryonal / drug therapy*,  physiopathology
Neuroblastoma / genetics
Rhabdomyosarcoma / genetics
Sarcoma, Ewing's / genetics
Telomerase / antagonists & inhibitors,  genetics,  physiology*
Telomere / drug effects,  metabolism*
Wilms Tumor / genetics
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase; EC 2.7.7.49/Tert protein, mouse

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