Targeting the telomere and shelterin complex for cancer therapy: current views and future perspectives
| Autor: | Alan Bilsland, W. Nicol Keith, Claire J. Cairney |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Telomerase
senescence DNA damage Telomere-Binding Proteins Reviews Apoptosis Biology telomerase Shelterin Complex 03 medical and health sciences 0302 clinical medicine Telomere Homeostasis Neoplasms cancer Humans Molecular Targeted Therapy Enzyme Inhibitors telosome targeting Cellular Senescence 030304 developmental biology Telomere-binding protein telomere 0303 health sciences novel therapeutics Cell Biology Shelterin Telomere Cell biology 030220 oncology & carcinogenesis Cancer cell Molecular Medicine Cell aging shelterin DNA Damage |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| Popis: | Aberrant telomere homeostasis is essential for cell immortality, enabling cells to evade telomere dependent senescence. Disruption of telomere structure and function in cancer cells is highly toxic as shown by detailed pre-clinical evaluation of telomerase inhibitors. Under telomerase inhibition, cells must divide sufficiently frequently to allow one or more telomeres to shorten to an unprotected length. Functioning telomeres are disguised from the DNA damage machinery by DNA remodelling and other activities of the telomere binding complex shelterin. Direct interference with shelterin has been shown to result in cell killing and small molecules directly targeting telomere DNA also have anti-tumour effects partially dependent on shelterin disruption. However, shelterin components have not generally been regarded as therapeutic targets in their own right. In this review, we explore the possibilities for therapeutic targeting of the shelterin complex. |
| Databáze: | OpenAIRE |
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