Abstract 2965: Olaparib and veliparib as effective PARP inhibitors for cancer prevention in a BRCA1-deficient mouse model

An inherited mutation in the BRCA1 gene leads to genomic instability and those with this mutation have a 50-80% risk for developing breast cancer by age 70. Though bilateral prophylactic mastectomy and surveillance are viable options for this high-risk population, chemoprevention may serve as a good alternative strategy. BRCA1 functions to repair double stranded DNA breaks via homologous recombination and as such, BRCA1 mutations force the cells to rely on other DNA repair mechanisms such as base excision repair, a process which requires Poly ADP ribose polymerase (PARP). Thus, PARP inhibition in BRCA1-deficient cells may induce apoptosis in these cells, which would otherwise develop into a tumor, while leaving normal cells intact. Olaparib and veliparib are promising PARP inhibitors that are currently in clinical trials for breast cancer treatment; however, their role in cancer prevention has not been examined. Hence, this study evaluated the effect of these PARP inhibitors in chemoprevention in the BrcaCo/Co;MMTV-Cre;p53+/- mouse model. Mice were fed continuously with olaparib (200 mg/kg diet) or veliparib (100 mg/kg diet) and tumor development was assessed. Both olaparib and veliparib significantly delayed tumor development by 6.5 and 2.4 weeks respectively (p Citation Format: Ciric To, Charlotte R. Williams, Darlene B. Royce, Ryan M. Collins, Michael B. Sporn, Karen T. Liby. Olaparib and veliparib as effective PARP inhibitors for cancer prevention in a BRCA1-deficient mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2965. doi:10.1158/1538-7445.AM2014-2965