Abstract
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.
Keywords: Cancer, child, telomere, novel therapies
Anti-Cancer Agents in Medicinal Chemistry
Title: Telomere Maintenance as Therapeutic Target in Embryonal Tumours
Volume: 10 Issue: 3
Author(s): T. Shalaby, E. Hiyama and M.A. Grotzer
Affiliation:
Keywords: Cancer, child, telomere, novel therapies
Abstract: 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.
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Cite this article as:
Shalaby T., Hiyama E. and Grotzer M.A., Telomere Maintenance as Therapeutic Target in Embryonal Tumours, Anti-Cancer Agents in Medicinal Chemistry 2010; 10 (3) . https://dx.doi.org/10.2174/1871520611009030196
DOI https://dx.doi.org/10.2174/1871520611009030196 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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