Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer

被引：7

作者：

Chen, Yi-xin ^{[1
,2
,3
]}

Tan, Li-ming ^{[4
]}

Gong, Jian-ping ^{[4
]}

Huang, Ma-sha ^{[1
,2
,3
]}

Yin, Ji-ye ^{[1
,2
,3
]}

Zhang, Wei ^{[1
,2
,3
]}

Zhou, Hong-hao ^{[1
,2
,3
]}

Liu, Zhao-qian ^{[1
,2
,3
]}

机构：

[1] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Hunan Key Lab Pharmacogenet, Changsha 410008, Peoples R China

[2] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Peoples R China

[3] Cent South Univ, Inst Clin Pharmacol, Engn Res Ctr Appl Technol Pharmacogen, Minist Educ, Changsha 410078, Peoples R China

[4] Second Peoples Hosp Huaihua City, Dept Pharm, Huaihua 418000, Peoples R China

来源：

ACTA PHARMACOLOGICA SINICA | 2021年 / 42卷 / 12期

基金：

中国国家自然科学基金;

关键词：

prostate cancer; PARP inhibitors; response prediction biomarkers; synergistic combination strategies; DNA-REPAIR DEFECTS; CELL-FREE DNA; POLY(ADP-RIBOSE) POLYMERASE; PATIENTS PTS; PHASE-II; HOMOLOGOUS RECOMBINATION; PEMBROLIZUMAB PEMBRO; DAMAGE RESPONSE; PLUS OLAPARIB; PTEN DELETION;

D O I：

10.1038/s41401-020-00604-1

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

PARP inhibitors are a group of inhibitors targeting poly(ADP-ribose) polymerases (PARP1 or PARP2) involved in DNA repair and transcriptional regulation, which may induce synthetic lethality in BRCAness tumors. Systematic analyzes of genomic sequencing in prostate cancer show that similar to 10%-19% of patients with primary prostate cancer have inactivated DNA repair genes, with a notably higher proportion of 23%-27% in patients with metastatic castration-resistant prostate cancer (mCRPC). These characteristic genomic alterations confer possible vulnerability to PARP inhibitors in patients with mCRPC who benefit only modestly from other therapies. However, only a small proportion of patients with mCRPC shows sensitivity to PARP inhibitors, and these sensitive patients cannot be fully identified by existing response prediction biomarkers. In this review, we provide an overview of the potential response prediction biomarkers and synergistic combinations studied in the preclinical and clinical stages, which may expand the population of patients with prostate cancer who may benefit from PARP inhibitors.

引用

页码：1970 / 1980

页数：11

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