Development of PARP and immune-checkpoint inhibitor combinations

Abstract

PARP inhibitors drive increased DNA damage, particularly in tumors with existing defects in DNA repair. This damage not only promotes immune priming through a range of molecular mechanisms, but also leads to adaptive upregulation of programmed death ligand 1 (PD-L1) expression. In this context, PARP inhibition and programmed cell death 1 (PD-1)/PD-L1–targeting antibodies represent a rationale combination. In this review, we detail the basic and translational science underpinning this promising new combination, summarize available clinical data, and discuss the key questions that remain to be addressed during future development.