Mechanisms and Clinical Practice of PARP1 Inhibitors for Synergistic Sensitization Therapy of Glioblastoma

This review discusses the potential of poly (ADP-ribose) polymerase-1 (PARP1) inhibition for enhancing temozolomide (TMZ) efficacy against glioblastoma multiforme (GBM) cells. Through the analysis of PARP1 repair in multiple DNA damage-response processes, including single-strand break repair (SSBR), replication stress, and mismatch repair (MMR), as well as the repair of TMZ-mediated damage, it can be concluded that PARP1 inhibition has a biological rationale for enhancing the effect of TMZ on GBM cells. Preclinical studies of the PARP1 inhibitors olaparib and talazoparib have shown that a PARP1 inhibitor plus TMZ combination can enhance TMZ-induced cytotoxicity and inhibit the survival of GBM cells. However, the clinical application of this strategy remains limited by insufficient clinical evidence and pharmacological barriers, such as hematological toxicity and restricted penetration of some PARP inhibitors across the blood-brain barrier (BBB). Therefore, future research directions should focus on improving sustained central nervous system exposure, optimizing combination regimens, and selecting sufficient samples. In these ways, the effectiveness of TMZ in treating GBM cells may be enhanced in clinical settings.