The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials

被引：12

作者：

Xia, Mingyue ^{[1
]}

Guo, Zhigang ^{[1
]}

Hu, Zhigang ^{[1
]}

机构：

[1] Nanjing Normal Univ, Coll Life Sci, Jiangsu Key Lab Mol & Med Biotechnol, 1 WenYuan Rd, Nanjing 210023, Peoples R China

来源：

BIOMOLECULES | 2021年 / 11卷 / 05期

基金：

中国国家自然科学基金;

关键词：

PARP inhibitors; synthetic lethality; prostate cancer (PC); the latest research progress; combination strategies; DNA-DAMAGE RESPONSE; BREAST-CANCER; POLY(ADP-RIBOSE) POLYMERASE; MAINTENANCE THERAPY; CHK1; INHIBITOR; PHASE-II; BMN; 673; REPAIR; OLAPARIB; OVARIAN;

D O I：

10.3390/biom11050722

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. Olaparib has been approved by the FDA for advanced ovarian and breast cancer with BRCA mutations, and as a maintenance therapy for ovarian cancer after platinum chemotherapy. PARPis are also a new and emerging clinical treatment for metastatic castration-resistant prostate cancer (mCRPC). Although PARPis have shown great efficacy, their widespread use is restricted by various factors, including drug resistance and the limited population who benefit from treatment. It is necessary to study the combination of PARPis and other therapeutic agents such as anti-hormone drugs, USP7 inhibitors, BET inhibitors, and immunotherapy. This article reviews the mechanism of PARP inhibition in the treatment of PC, the progress of clinical research, the mechanisms of drug resistance, and the strategies of combination treatments.

引用

页数：16

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