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Int. J. Mol. Sci. 2018, 19(10), 3249; https://doi.org/10.3390/ijms19103249

Translational Research Opportunities Regarding Homologous Recombination in Ovarian Cancer

1
Medical Oncology Department, B-ARGO Group, Institut Català d’Oncologia Badalona, Carretera del Canyet s/n, 08916 Badalona, Spain
2
Campus de la UAB, Universitat Autónoma de Barcelona, Plaça Cívica, 08193 Bellaterra, Spain
3
Health Sciences Research Institute of the Germans Trias i Pujol Foundation (IGTP), B-ARGO Group, Carretera del Canyet s/n, 08916 Badalona, Spain
4
Program against Cancer Therapeutic Resistance (ProCURE), Institut Català d’Oncologia Badalona, Program for Predictive and Personalized Cancer Medicine (PMPPC), Health Sciences Research Institute Germans Trias i Pujo (IGTP), Carretera de Can Ruti, Camí de les Escoles s/n, 08916 Badalona, Spain
5
Gynecology Department, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain
6
Institut de Recerca contra la Leucemia Josep Carreras, 08916 Badalona, Spain
*
Author to whom correspondence should be addressed.
Received: 29 September 2018 / Revised: 29 September 2018 / Accepted: 16 October 2018 / Published: 19 October 2018
(This article belongs to the Special Issue Ovarian Cancer: Pathogenesis, Diagnosis, and Treatment)
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PDF [289 KB, uploaded 19 October 2018]

Abstract

Homologous recombination (HR) is a DNA repair pathway that is deficient in 50% of high-grade serous ovarian carcinomas (HGSOC). Deficient HR (DHR) constitutes a therapeutic opportunity for these patients, thanks to poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi; olaparib, niraparib, and rucaparib are already commercialized). Although initially, PARPi were developed for patients with BRCA1/2 mutations, robust clinical data have shown their benefit in a broader population without DHR. This breakthrough in daily practice has raised several questions that necessitate further research: How can populations that will most benefit from PARPi be selected? At which stage of ovarian cancer should PARPi be used? Which strategies are reasonable to overcome PARPi resistance? In this paper, we present a summary of the literature and discuss the present clinical research involving PARPi (after reviewing ClinicalTrials.gov) from a translational perspective. Research into the functional biomarkers of DHR and clinical trials testing PARPi benefits as first-line setting or rechallenge are currently ongoing. Additionally, in the clinical setting, only secondary restoring mutations of BRCA1/2 have been identified as events inducing resistance to PARPi. The clinical frequency of this and other mechanisms that have been described in preclinics is unknown. It is of great importance to study mechanisms of resistance to PARPi to guide the clinical development of drug combinations. View Full-Text
Keywords: ovarian cancer; high-grade serous ovarian cancer; deficient homologous recombination; PARP inhibitors; BRCA1; BRCA2; mechanisms of resistance ovarian cancer; high-grade serous ovarian cancer; deficient homologous recombination; PARP inhibitors; BRCA1; BRCA2; mechanisms of resistance
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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Romeo, M.; Pardo, J.C.; Martínez-Cardús, A.; Martínez-Balibrea, E.; Quiroga, V.; Martínez-Román, S.; Solé, F.; Margelí, M.; Mesía, R. Translational Research Opportunities Regarding Homologous Recombination in Ovarian Cancer. Int. J. Mol. Sci. 2018, 19, 3249.

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