PARP and DNA Repair
It has been identified that approximately 50% of high-grade serous ovarian cancers exhibit defects in homologous recombination and DNA repair pathways, many of which could be susceptible to targeting with PARP inhibition.1 While tumor cells with BRCA1 or BRCA2 deficiencies are exquisitely sensitive to PARP inhibition, PARP inhibitors may have activity in tumor cells deficient in other DNA repair mechanisms or in combination with DNA-damaging chemotherapy.2,3
Ovarian cancer is the fifth leading cause of cancer death in women in the United States and the eighth leading cause of cancer death in women globally.4,5 The 5-year relative survival rate for all stages of ovarian cancer in the US is approximately 45%.6
The vast majority of ovarian cancers are high-grade serous carcinomas (HGSCs).7 These are aggressive tumors and account for approximately 70% of deaths due to ovarian cancer.1,7
While approximately 13% of HGSCs result from germline mutations in BRCA1/2, an integrated genomic analysis demonstrated that TP53 was mutated in at least 96% of HGSC samples. Cancer-related signaling pathways that were dysregulated included the RB1 (67%), PI3K/RAS (45%) and homologous recombination (HR) pathways (~50%).1
The risk of developing ovarian cancer may be increased in women with BRCA1/2 mutations. Ovarian cancer penetrance is 41% to 46% for BRCA1 and 17% to 23% for BRCA2 mutations.8
AbbVie is committed to helping address these challenges and is actively conducting research in this area to help address this unmet need.