SYNVIA
Financiado
Synthetic viability of homologous recombination deficient cancers
Although various effective anti-cancer drug treatments have become available over the last decades, drug resistance remains the major cause of death of cancer patients. Striking examples are patients with tumors that are defective...
Although various effective anti-cancer drug treatments have become available over the last decades, drug resistance remains the major cause of death of cancer patients. Striking examples are patients with tumors that are defective in DNA repair by homologous recombination (HR). Despite initial responses to cancer therapy, resistance of primary or disseminated tumors eventually emerges, which minimizes therapeutic options and greatly reduces survival. The molecular mechanisms underlying this therapy escape are often poorly understood.
In the SYNVIA project I will address the problem of therapy escape by using powerful genetically engineered mouse models for BRCA1- and BRCA2-deficient breast cancer, which closely mimic the human disease. Due to the BRCA inactivation, the tumors that arise lack HR-directed DNA repair. Similar to the situation in cancer patients, we observe that cancer cells in these models eventually escape the deadly effects of chemotherapy or novel targeted drugs. Thus, these resistance models provide a unique opportunity to explore therapy escape mechanisms.
I propose an approach that will take the in vivo analysis of therapy resistance mechanisms to a new level. By synergizing the advantages of next generation sequencing with functional genetic screens in tractable model systems, I will explore novel mechanisms that cause resistance of HR-deficient cancers by the loss of another gene (synthetic viability). I provide evidence that new mechanisms of resistance can be identified with this approach. In an innovative step, I will generate genome-wide alterations using the revolutionizing CRISPR/Cas technology. Mutations will also be introduced into 3D tumor organoid cultures, as we found that these are more physiologically relevant. I am convinced that the combination of these state-of-the-art approaches will yield highly useful information for designing effective approaches to circumvent or reverse therapy escape in human cancer patients.
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Duración del proyecto: 62 meses
Fecha Inicio: 2016-04-13
Fecha Fin: 2021-06-30
Fecha Fin: 2021-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-06-30
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-CoG-2015:
ERC Consolidator Grant
Cerrada
hace 9 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
UNIVERSITAET BERN
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
2.14M€ |
Participante