Advances in the use of PARP inhibitors for BRCA1/2-associated breast cancer: talazoparib.

Poly-ADP-ribosyl polymerase (PARP) enzymes PARP-1 and PARP-2 recognize DNA damage and set off a cascade of cellular mechanisms required for multiple types of DNA damage repair. PARP inhibitors are small molecule mimetics of nicotinamide which bind to PARP's catalytic domain to inhibit poly-ADP-ribosylation (PARylation) of target proteins, including PARP-1 itself. PARP inhibitors olaparib, veliparib, talazoparib, niraparib and rucaparib have predominantly been studied in women with breast or ovarian cancers associated with deleterious germline mutations in BRCA1 and BRCA2 (gBRCA1/2+). The BRCA1 and BRCA2 proteins are involved in DNA repair by homologous recombination. This review will focus on talazoparib, a PARP inhibitor approved by the US FDA for the treatment of metastatic gBRCA1/2+ breast cancers in October 2018.