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Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations

High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcription...

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Autores principales: Madariaga, Ainhoa, Lheureux, Stephanie, Oza, Amit M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468364/
https://www.ncbi.nlm.nih.gov/pubmed/30909618
http://dx.doi.org/10.3390/cancers11030416
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author Madariaga, Ainhoa
Lheureux, Stephanie
Oza, Amit M.
author_facet Madariaga, Ainhoa
Lheureux, Stephanie
Oza, Amit M.
author_sort Madariaga, Ainhoa
collection PubMed
description High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.
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spelling pubmed-64683642019-04-24 Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations Madariaga, Ainhoa Lheureux, Stephanie Oza, Amit M. Cancers (Basel) Review High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers. MDPI 2019-03-23 /pmc/articles/PMC6468364/ /pubmed/30909618 http://dx.doi.org/10.3390/cancers11030416 Text en © 2019 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
Madariaga, Ainhoa
Lheureux, Stephanie
Oza, Amit M.
Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations
title Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations
title_full Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations
title_fullStr Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations
title_full_unstemmed Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations
title_short Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations
title_sort tailoring ovarian cancer treatment: implications of brca1/2 mutations
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468364/
https://www.ncbi.nlm.nih.gov/pubmed/30909618
http://dx.doi.org/10.3390/cancers11030416
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