Innovating Works

PARPinhibit

Financiado
A systems biology approach to tackle PARP inhibitors resistance and identify nov...
A systems biology approach to tackle PARP inhibitors resistance and identify novel therapeutic targets to overcome it Inhibition of PARP1 in cancer therapy is a recently adopted strategy to treat cancers where DNA repair is defective, such as breast and ovarian cancer caused by mutations in BRCA1 or BRCA2. In addition, PARP1 inhibitors (PARPi) ca... Inhibition of PARP1 in cancer therapy is a recently adopted strategy to treat cancers where DNA repair is defective, such as breast and ovarian cancer caused by mutations in BRCA1 or BRCA2. In addition, PARP1 inhibitors (PARPi) can be useful even in the absence of BRCA mutations, likely due to pathogenic variants or epigenetic inactivation of other DNA repair related genes. However, development of resistance to PARPi is a significant challenge. To address this challenge, I propose to identify proteins that modulate PARP1 activity that could be used as additional therapeutic targets. The strength of this project is based on a systems biology overall strategy exploiting multiple independent datasets to identify candidates protein interactors, followed by a rigorous biochemical and genetic approach to characterize this interaction. Analysis of identified proteins and their role in PARPi resistance will be achieved at three main levels: a) in-silico and molecular studies of the interaction; b) influence on PARP1 activity and role in PARPi resistance after CRISPR-cas9 editing; c) expression levels in breast and ovarian cancer tissues. Results from this project will illuminate mechanisms of PARPi resistance and generate potential targets for therapy in breast and ovarian cancer. These results will contribute to the reduction in mortality due to breast and ovarian cancer and they will give an answer to this world-wide diffuse challenge. ver más
30/12/2023
CNR
251K€
Duración del proyecto: 57 meses Fecha Inicio: 2019-03-27
Fecha Fin: 2023-12-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2023-12-30
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
Presupuesto El presupuesto total del proyecto asciende a 251K€
Líder del proyecto
CONSIGLIO NAZIONALE DELLE RICERCHE No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5