PURPOSE OF REVIEW: The recent United States Food and Drug Administration 
approvals of niraparib and olaparib as maintenance monotherapy for 
platinum-sensitive, high-grade ovarian cancers independent of BRCA status 
reflect a willingness to seek indications for poly-ADP-ribose polymerase (PARP) 
inhibitors beyond cancers with deleterious breast cancer 1 and breast cancer 2 
mutations. In this review, I describe the rationale behind current PARP 
combination clinical trials with chemotherapies, angiogenesis inhibitors, cell 
cycle checkpoint inhibitors, and inhibitors of the phosphoinositide 3-kinase/AK 
thymoma/mechanistic target of rapamycin pathway.
RECENT FINDINGS: PARP inhibitors have primarily been studied as monotherapy in 
cancers with homologous recombination repair defects based on an early 
understanding of PARP-1 as a base excision repair enzyme and the idea that 
abrogation of two DNA repair pathways cripples rapidly dividing cancer cells. It 
is now known that PARP-1 is a DNA damage sensor with much wider reaching roles 
in DNA repair processes and normal cellular functions, opening possibilities for 
PARP inhibitor use in other clinical contexts.
SUMMARY: PARP inhibitor combination clinical trials are in the early stages, but 
will deepen our understanding of DNA repair mechanisms, cancer biology, and 
targeted therapies, thus contributing to the next iteration of therapeutic 
options for our patients.