Introduction
death, tumour
DNA DAMAGE, TUMOUR, SOLID TUMOUR
PARP 1/2 inhibitors interfere with DNA repair mechanisms by binding directly to PARP enzymes, thereby inhibiting their activity, and through trapping PARP-DNA complexes at the site of DNA damage. These effects lead to genomic instability, prevention of DNA transcription/translation, increased DNA damage, and tumour cell death [PARP inhibitors may enhance the antitumour effects of immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors [Preclinical studies suggest addition of a PD-(L)1 inhibitor can resensitise cells treated with PARP inhibitors to T-cell cytotoxicity, which restores the reduced antitumour immunity caused by upregulation of PD-L1 expression and enhances antitumour activity [Pamiparib (developed by BeiGene, Ltd.) is a potent, selective, investigational small molecule inhibitor of PARP1 and PARP2 that has demonstrated brain penetration and PARP-DNA complex trapping in preclinical studies [Several PD-(L)1 inhibitors are approved as monotherapy and/or in combination with chemotherapy and/or other agents for the treatment of a range of solid tumours, with survival benefits demonstrated versus placebo and various other comparators [A phase Ia/b study was initiated to investigate the combination of pamiparib with tislelizumab in patients with advanced solid tumours [