Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, 
formerly known as AG014699 and PF-01367338) for the treatment of sporadic 
ovarian cancer. We studied the growth inhibitory effects of rucaparib in a panel 
of 39 ovarian cancer cell lines that were each characterized for mutation and 
methylation status of BRCA1/2, baseline gene expression signatures, copy number 
variations of selected genes, PTEN status, and sensitivity to platinum-based 
chemotherapy. To study interactions with chemotherapy, we used multiple drug 
effect analyses and assessed apoptosis, DNA fragmentation, and γH2AX formation. 
Concentration-dependent antiproliferative effects of rucaparib were seen in 26 
of 39 (67%) cell lines and were not restricted to cell lines with BRCA1/2 
mutations. Low expression of other genes involved in homologous repair (e.g., 
BCCIP, BRCC3, ATM, RAD51L1), amplification of AURKA or EMSY, and response to 
platinum-based chemotherapy was associated with sensitivity to rucaparib. Drug 
interactions with rucaparib were synergistic for topotecan, synergistic, or 
additive for carboplatin, doxorubicin or paclitaxel, and additive for 
gemcitabine. Synergy was most pronounced when rucaparib was combined with 
topotecan, which resulted in enhanced apoptosis, DNA fragmentation, and γH2AX 
formation. Importantly, rucaparib potentiated chemotherapy independent of its 
activity as a single agent. PARP inhibition may be a useful therapeutic strategy 
for a wider range of ovarian cancers bearing deficiencies in the homologous 
recombination pathway other than just BRCA1/2 mutations. These results support 
further clinical evaluation of rucaparib either as a single agent or as an 
adjunct to chemotherapy for the treatment of sporadic ovarian cancer.