PARP

PARP stands for poly(ADP-ribose) polymerase, a family of enzymes that catalyze the addition of poly(ADP-ribose) chains onto proteins using nicotinamide adenine dinucleotide (NAD+) as a substrate. In humans, the best-studied members are PARP1, PARP2, and PARP3, which are predominantly nuclear and are activated by DNA strand breaks. When activated, PARP enzymes synthesize long and branched PAR chains and often auto-modify themselves, which helps recruit DNA repair factors to damaged sites and modulates chromatin structure.

Biological roles include base excision repair and single-strand break repair, maintenance of genome stability, and coordination of replication fork progression. PARP activity also participates in transcription regulation and inflammatory signaling, with broader effects on cell survival after DNA damage.

PARP inhibitors are a class of anticancer drugs that block catalytic activity and can trap PARP on DNA, increasing cytotoxicity in certain cancer cells. They are particularly effective in tumors deficient in homologous recombination repair, such as BRCA1 or BRCA2 mutation carriers. Approved PARP inhibitors include olaparib, niraparib, rucaparib, and talazoparib, with approved indications in ovarian, breast, pancreatic, and prostate cancers, among others. Combination approaches with platinum chemotherapy or immune checkpoint inhibitors are under investigation.

Most PARP biology centers on PARP1 and PARP2; PARP3 and other family members like tankyrases regulate distinct processes. Therapeutic resistance can arise through restoration of BRCA function, loss of PARP trapping, or activation of alternative repair pathways. Side effects of PARP inhibitors commonly include anemia and thrombocytopenia, and patient management requires monitoring.