Recent findings indicate that a major mechanism by which poly(ADP-ribose) 
polymerase (PARP) inhibitors kill cancer cells is by trapping PARP1 and PARP2 to 
the sites of DNA damage. The PARP enzyme-inhibitor complex "locks" onto damaged 
DNA and prevents DNA repair, replication, and transcription, leading to cell 
death. Several clinical-stage PARP inhibitors, including veliparib, rucaparib, 
olaparib, niraparib, and talazoparib, have been evaluated for their 
PARP-trapping activity. Although they display similar capacity to inhibit PARP 
catalytic activity, their relative abilities to trap PARP differ by several 
orders of magnitude, with the ability to trap PARP closely correlating with each 
drug's ability to kill cancer cells. In this article, we review the available 
data on molecular interactions between these clinical-stage PARP inhibitors and 
PARP proteins, and discuss how their biologic differences might be explained by 
the trapping mechanism. We also discuss how to use the PARP-trapping mechanism 
to guide the development of PARP inhibitors as a new class of cancer therapy, 
both for single-agent and combination treatments.