Clinical application of PARP inhibitors in ovarian cancer: from molecular mechanisms to the current status

Journal of Ovarian Research

Review

Jiani Yang¹  Yu Wang¹  Yongsong Wu²  Shilin Xu³  Shanshan Cheng³ 

[1]Department of Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai200092, China

[2]Department of Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai200092, China

[3]Obstetrics and Gynecology, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China

[4]Obstetrics and Gynecology, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China

关键词: PARP inhibitor;    Ovarian cancer;    BRCA;    Synthetic lethality;    Homologous recombination repair;    Chemotherapy resistance;    Biomarkers;    Side effect;   

DOI  :  10.1186/s13048-023-01094-5

 received in 2022-08-24, accepted in 2023-01-02,  发布年份 2023

来源: Springer

【 摘 要 】

As a kind of gynecological tumor, ovarian cancer is not as common as cervical cancer and breast cancer, but its malignant degree is higher. Despite the increasingly mature treatment of ovarian cancer, the five-year survival rate of patients is still less than 50%. Based on the concept of synthetic lethality, poly (ADP- ribose) polymerase (PARP) inhibitors target tumor cells with defects in homologous recombination repair(HRR), the most significant being the target gene Breast cancer susceptibility genes(BRCA). PARP inhibitors capture PARP-1 protein at the site of DNA damage to destroy the original reaction, causing the accumulation of PARP-DNA nucleoprotein complexes, resulting in DNA double-strand breaks(DSBs) and cell death. PARP inhibitors have been approved for the treatment of ovarian cancer for several years and achieved good results. However, with the widespread use of PARP inhibitors, more and more attention has been paid to drug resistance and side effects. Therefore, further research is needed to understand the mechanism of PARP inhibitors, to be familiar with the adverse reactions of the drug, to explore the markers of its efficacy and prognosis, and to deal with its drug resistance. This review elaborates the use of PARP inhibitors in ovarian cancer.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 10

Fig. 3

Fig. 4