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Open AccessReview

Wise Management of Ovarian Cancer: On the Cutting Edge

1
Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent ME7 5NY, UK
2
AELIA Organization, 9th Km Thessaloniki—Thermi, 57001 Thessaloniki, Greece
3
St Luke’s Cancer Center, Royal Surrey County Hospital, Egerton Rd, Guildford GU2 7XX, UK
4
Division of Gynecology, University Hospital Zurich, Frauenklinikstrasse 10, CH-8091 Zürich, Switzerland
5
Department of Oncology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, P.O. Box 100, FI-00029 Helsinki, Finland
6
Cambridge University Hospitals NHS Foundation Trust, Hills Rd, Cambridge CB2 0QQ, UK
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Department of Cancer Medicine, Gustave Roussy Institut, 94805 Villejuif, France
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Department of Hematology-Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut 166830, Lebanon
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Medical School, University of Ioannina, Stavros Niarchou Avenue, 45110 Ioannina, Greece
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2020, 10(2), 41; https://doi.org/10.3390/jpm10020041
Received: 29 April 2020 / Revised: 13 May 2020 / Accepted: 19 May 2020 / Published: 21 May 2020
(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations. View Full-Text
Keywords: ovarian cancer; next-generation sequencing; homologous recombination repair; PARP inhibitors; AURK inhibitors; metformin; personalized treatment ovarian cancer; next-generation sequencing; homologous recombination repair; PARP inhibitors; AURK inhibitors; metformin; personalized treatment
MDPI and ACS Style

Boussios, S.; Mikropoulos, C.; Samartzis, E.; Karihtala, P.; Moschetta, M.; Sheriff, M.; Karathanasi, A.; Sadauskaite, A.; Rassy, E.; Pavlidis, N. Wise Management of Ovarian Cancer: On the Cutting Edge. J. Pers. Med. 2020, 10, 41.

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