Advances in poly (ADP-ribose) polymerase inhibitors / 中国肿瘤临床

ABSTRACT

Genomic instability with increased DNA damage accumulations and partial DNA repair defects is more dependent on exist-ing DNA repair pathways, leading to disturbance in restoration of completely chemoradiation-induced DNA damage and finally induc-ing resistance to chemoradiation. The discovery of poly (ADP-ribose) polymerase inhibitors (PARPis) has sparked interest in synergistic reactions to kill tumor cells that are deficient in homologous recombination repair. Currently, under FDA approval of PARPis on ad-vanced ovarian cancer, clinical trials for several PARPis are being conducted to assess toxicities, efficacies, and benefits of drugs as monotherapy or in combination with radiation or other chemotherapeutic agents for ovarian, breast, prostate, rectal, lung, pancreatic, peritoneal, head and neck, and brain cancers;squamous cell carcinomas;sarcomas;and others. In this review, we focus on outlining the molecular mechanisms and clinical developments of approved PARPis and the emerging confusions in ongoing clinical trials and practice.