Identifying Determinants of PARP Inhibitor Sensitivity in Ovarian Cancer
Abstract
We hypothesize that a range of common ovarian cancer predisposing germ-line BRCA1 gene mutations produce semi-functional proteins that are capable of providing PARP inhibitor resistance. Gene mutations that result in the activation of DNA end resection are likely to be required for restoration of HR DNA repair in this setting. Additionally, genetic events that stabilize mutant BRCA1 proteins may be required to avoid proteasome-mediated degradation. Our objectives are to define the BRCA1 peptide region minimally required for PARP inhibitor resistance, and discover genetic alterations that activate DNA end resection as well as mutant BRCA1 protein stabilization in ovarian carcinomas. The expression of mutant BRCA1 or novel proteins identified to be important for drug resistance will be assessed for their ability to be used as biomarkers of PARP inhibitor or platinum response. Protein expression in tumors will be assessed for their potential to serve as biomarkers that predict PARP inhibitor or platinum response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1002904
Entities
People
- Neil F. Johnson