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The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications o...

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Autores principales: Dion, Ludivine, Carton, Isis, Jaillard, Sylvie, Nyangoh Timoh, Krystel, Henno, Sébastien, Sardain, Hugo, Foucher, Fabrice, Levêque, Jean, de la Motte Rouge, Thibault, Brousse, Susie, Lavoué, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408825/
https://www.ncbi.nlm.nih.gov/pubmed/32679669
http://dx.doi.org/10.3390/jcm9072239
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author Dion, Ludivine
Carton, Isis
Jaillard, Sylvie
Nyangoh Timoh, Krystel
Henno, Sébastien
Sardain, Hugo
Foucher, Fabrice
Levêque, Jean
de la Motte Rouge, Thibault
Brousse, Susie
Lavoué, Vincent
author_facet Dion, Ludivine
Carton, Isis
Jaillard, Sylvie
Nyangoh Timoh, Krystel
Henno, Sébastien
Sardain, Hugo
Foucher, Fabrice
Levêque, Jean
de la Motte Rouge, Thibault
Brousse, Susie
Lavoué, Vincent
author_sort Dion, Ludivine
collection PubMed
description Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20–30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management.
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spelling pubmed-74088252020-08-13 The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer Dion, Ludivine Carton, Isis Jaillard, Sylvie Nyangoh Timoh, Krystel Henno, Sébastien Sardain, Hugo Foucher, Fabrice Levêque, Jean de la Motte Rouge, Thibault Brousse, Susie Lavoué, Vincent J Clin Med Review Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20–30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management. MDPI 2020-07-15 /pmc/articles/PMC7408825/ /pubmed/32679669 http://dx.doi.org/10.3390/jcm9072239 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Dion, Ludivine
Carton, Isis
Jaillard, Sylvie
Nyangoh Timoh, Krystel
Henno, Sébastien
Sardain, Hugo
Foucher, Fabrice
Levêque, Jean
de la Motte Rouge, Thibault
Brousse, Susie
Lavoué, Vincent
The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer
title The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer
title_full The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer
title_fullStr The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer
title_full_unstemmed The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer
title_short The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer
title_sort landscape and therapeutic implications of molecular profiles in epithelial ovarian cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408825/
https://www.ncbi.nlm.nih.gov/pubmed/32679669
http://dx.doi.org/10.3390/jcm9072239
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