Current status of poly(ADP-ribose) polymerase inhibitors and future directions.

ABSTRACT: Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer. Clinical trials of various combinations of PARP inhibitors with cytotoxic or molecular-targeted agents are also underway. In particular, expanded applications

SUBMITTER: Ohmoto A 

PROVIDER: S-EPMC5667784 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature