PARP Inhibitors in Ovarian Cancer: The Route to "Ithaca"

被引：64

作者：

Boussios, Stergios ^{[1
,2
]}

Karathanasi, Afroditi ^{[1
]}

Cooke, Deirdre ^{[1
]}

Neille, Cherie ^{[1
]}

Sadauskaite, Agne ^{[3
]}

Moschetta, Michele ^{[4
]}

Zakynthinakis-Kyriakou, Nikolaos ^{[5
]}

Pavlidis, Nicholas ^{[6
]}

机构：

[1] Medway NHS Fdn Trust, Acute Oncol Assessment Unit, Windmill Rd, Gillingham ME7 5NY, Kent, England

[2] AELIA Org, 9th Km Thessaloniki Thermi, Thessaloniki 57001, Greece

[3] Medway NHS Fdn Trust, Dept Pharm, Windmill Rd, Gillingham ME7 5NY, Kent, England

[4] Sarah Cannon Res Inst, Drug Dev Unit, 93 Harley St, London W1G 6AD, England

[5] Leicester Diabet Res Ctr, Gwendolen Rd, Leicester LE5 4PW, Leics, England

[6] Univ Ioannina, Med Sch, Stavros Niarchou Ave, GR-45110 Ioannina, Greece

来源：

DIAGNOSTICS | 2019年 / 9卷 / 02期

关键词：

ovarian cancer; BRCA; PARP inhibitors; homologous recombination; companion diagnostic; toxic effects; resistance mechanism; POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; HOMOLOGOUS-RECOMBINATION-DEFICIENT; OLAPARIB MAINTENANCE THERAPY; GRADE SEROUS OVARIAN; DNA-REPAIR; PHASE-I; EPITHELIAL OVARIAN; OPEN-LABEL; GENOMIC INSTABILITY; ANTITUMOR-ACTIVITY;

D O I：

10.3390/diagnostics9020055

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Early studies have shown significant efficacy for PARP inhibitors in patients with germline breast related cancer antigens 1 and 2 (BRCA1/2) mutations. It has also become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this treatment. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The choice of which PARP inhibitor is mainly based upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of patients most likely to benefit from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The aim of this review is to describe the current evidence for PARP inhibitors in ovarian cancer, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolution of resistance.

引用

页数：29

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