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PARP Inhibitors in Ovarian Cancer: The Route to “Ithaca”

1
Acute Oncology Assessment Unit, Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent ME7 5NY, UK
2
AELIA Organization, 9th Km Thessaloniki—Thermi, 57001 Thessaloniki, Greece
3
Department of Pharmacy, Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent ME7 5NY, UK
4
Drug Development Unit, Sarah Cannon Research Institute, 93 Harley Street, London W1G 6AD, UK
5
Leicester Diabetes Research Centre, Gwendolen Road, Leicester LE5 4PW, UK
6
Medical School, University of Ioannina, Stavros Niarchou Avenue, 45110 Ioannina, Greece
*
Author to whom correspondence should be addressed.
Diagnostics 2019, 9(2), 55; https://doi.org/10.3390/diagnostics9020055
Received: 22 April 2019 / Revised: 12 May 2019 / Accepted: 16 May 2019 / Published: 18 May 2019
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
PDF [463 KB, uploaded 18 May 2019]

Abstract

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.
Keywords: ovarian cancer; BRCA; PARP inhibitors; homologous recombination; companion diagnostic; toxic effects; resistance mechanism ovarian cancer; BRCA; PARP inhibitors; homologous recombination; companion diagnostic; toxic effects; resistance mechanism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Boussios, S.; Karathanasi, A.; Cooke, D.; Neille, C.; Sadauskaite, A.; Moschetta, M.; Zakynthinakis-Kyriakou, N.; Pavlidis, N. PARP Inhibitors in Ovarian Cancer: The Route to “Ithaca”. Diagnostics 2019, 9, 55.

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