PARP Inhibitors: Strategic Use and Optimal Management in Ovarian Cancer

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors have become an established part of the anticancer armamentarium. Discovered in the 1980s, PARP inhibitors (PARPis) were initially developed to exploit the presence of BRCA mutations, which disrupt the homologous recombination repair of deoxyribonucleic acid (DNA) via synthetic lethality, an intrinsic vulnerability caused by the cell’s dependence on other DNA repair mechanisms for which PARP is an essential contributor. PARPi use expanded with the demonstration of clinical benefit when other mechanisms of high-fidelity DNA damage response were present in cancer cells called homologous repair deficiency (HRD). Recently, new data have resulted in the voluntary withdrawal of later-line treatment indications for all the available PARPis used in ovarian cancer because of a negative impact on overall survival (OS). PARPi switch maintenance to consolidate a response to platinum-based therapy is recommended for earlier treatment lines to have the greatest impact on the chance of cure and length of survival. This article reviews the clinical utility of PARPis and how to integrate them into best practices.