SHELTERINS
Financiado
Targeting Shelterin Proteins in Cancer
Telomeres are protective structures at the chromosome ends essential for genome stability. Telomere biology is intricately linked with human cancer. Most cancer cells reactivate telomerase to avoid telomere loss associated to cell...
Telomeres are protective structures at the chromosome ends essential for genome stability. Telomere biology is intricately linked with human cancer. Most cancer cells reactivate telomerase to avoid telomere loss associated to cell division. Targeting telomerase inhibition in cancer has shown very limited efficacy, alternative or additional mechanisms of telomere maintenance are thus at play in cancer. Recent evidence shows that components of the telomere-protecting shelterin complex are mutated in cancer. Shelterin prevents chromosome fusions, impedes persistent DNA damage response at telomeres and regulates telomerase activity. We were first in describing shelterin mutations in cancer and pioneered the idea of targeting shelterin as an anticancer strategy to induce length-idependent telomere damage. We also found that key cancer pathways regulate shelterin function throughout post-transcriptional modifications.
Developing new therapeutic approaches based on targeting shelterin is hampered by lack of mouse models and incomplete understanding of which underlying mechanisms mutations in shelterin drive tumour development. We strive to establish a comprehensive set of tools, to enable us to conduct a fundamental and far-reaching experimental programme on the role of shelterin in cancer. Our specific aims are to i) generate knock-in mice to understand the role of POT1 shelterin mutations found in cancer and develop personalized therapeutic strategies based on these alterations, ii) generate knock-in mice to understand the role of post-translational modifications of the TRF1 shelterin by several cancer pathways for the identification of new cancer targets, and iii) dissect the potential role of TRF1 in cancer stem cells. We expect to block the ability of cancer cells to divide indefinitely and effectively impair cancer growth. Our research programme will reveal the role of two fundamental aspects of biology, telomere capping and chromosomal stability, in cancer.
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Duración del proyecto: 60 meses
Fecha Inicio: 2020-06-22
Fecha Fin: 2025-06-30
Fecha Fin: 2025-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-06-22
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2019-ADG:
ERC Advanced Grant
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIO...
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Perfil tecnológico
TRL
4-5
18M
Perfil tecnológico
TRL
4-5
18M