Investigation of a Novel PARP Inhibitor PET Tracer in Ovarian Carcinoma
Abstract
Epithelial ovarian carcinomas are amongst the most deadly gynecologic cancers due to their insidious onset, lack of efficient screening methods, and late presentation. Approximately 10 percent of epithelial ovarian carcinomas have germline mutations in Breast Cancer Susceptibility Genes 1/2 (BRCA1/2) which are genes responsible for encoding primary DNA-repair proteins necessary for homologous recombination (HR). Furthermore, approximately 50-60 percent of non-BRCA1/2 related ovarian carcinomas have functional defects in HR (HRD) and behave phenotypically like BRCA1/2-related tumors due to genetic/epigenetic events. There is now substantial data that DNA-damaging chemotherapy +/- poly (ADP-ribose) polymerase-1 (PARP) inhibitors may be highly effective in BRCA-related cancers by exploiting the inherent HRD. However, clinical trials of PARPi in unselected ovarian cancer patients, alone or combined with other DNA damaging agents, have shown mixed response rates. A potential explanation for the disappointing results is the lack of an effective biomarker for functional HRD to predict benefit from PARPi or DNA-damaging agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2022
- Accession Number
- AD1229817
Entities
People
- Fiona Simpkins
Organizations
- University of Pennsylvania