A systems biology approach to tackle PARP-inhibitors resistance and identify novel therapeutic targets to overcome it - PARPinhibit (DSB.AD006.259)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of clinical physiology (IFC)

Project manager

ALVARO GALLI
Phone number: 0503153094
Email: alvaro.galli@ifc.cnr.it

Abstract

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.

Start date of activity

26/03/2020

Keywords

Molecular interactions, Molecular genetics, reverse genetics and RNAi, Personalised medicine

Last update: 14/05/2024