Development of poly(ADP-ribose) polymerase inhibitor and immunotherapy combinations: progress, pitfalls, and promises

The efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) is restricted by inevitable drug resistance, while their use in combination with chemotherapy and targeted agents is commonly associated with dose-limiting toxicities. Immune checkpoint blockade (ICB) has demonstrated durable responses in different solid tumors and is well-established across multiple cancers. Despite this, single agent activity is limited to a minority of patients and drug resistance remains an issue. Building on the monotherapy success of both drug classes, combining PARPi with ICB may be a safe and well-tolerated strategy with the potential to improve survival outcomes. In this review, we present the preclinical, translational, and clinical data supporting the combination of DNA damage response (DDR) and ICB as well as consider important questions to be addressed with future research.