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Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic cancer in the United States. Genomic analysis revealed roughly half of HGSOC display homologous repair deficiencies. An improved understanding of the genomic and somatic mutations that influence DNA repair led to the develo...

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Autores principales: Bouberhan, Sara, Philp, Lauren, Hill, Sarah, Al-Alem, Linah F., Rueda, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281458/
https://www.ncbi.nlm.nih.gov/pubmed/32403357
http://dx.doi.org/10.3390/cancers12051206
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author Bouberhan, Sara
Philp, Lauren
Hill, Sarah
Al-Alem, Linah F.
Rueda, Bo
author_facet Bouberhan, Sara
Philp, Lauren
Hill, Sarah
Al-Alem, Linah F.
Rueda, Bo
author_sort Bouberhan, Sara
collection PubMed
description High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic cancer in the United States. Genomic analysis revealed roughly half of HGSOC display homologous repair deficiencies. An improved understanding of the genomic and somatic mutations that influence DNA repair led to the development of poly(ADP-ribose) polymerase inhibitors for the treatment of ovarian cancer. In this review, we explore the preclinical and clinical studies that led to the development of FDA approved drugs that take advantage of the synthetic lethality concept, the implementation of the early phase trials, the development of companion diagnostics and proposed mechanisms of resistance.
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spelling pubmed-72814582020-06-19 Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer Bouberhan, Sara Philp, Lauren Hill, Sarah Al-Alem, Linah F. Rueda, Bo Cancers (Basel) Review High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic cancer in the United States. Genomic analysis revealed roughly half of HGSOC display homologous repair deficiencies. An improved understanding of the genomic and somatic mutations that influence DNA repair led to the development of poly(ADP-ribose) polymerase inhibitors for the treatment of ovarian cancer. In this review, we explore the preclinical and clinical studies that led to the development of FDA approved drugs that take advantage of the synthetic lethality concept, the implementation of the early phase trials, the development of companion diagnostics and proposed mechanisms of resistance. MDPI 2020-05-11 /pmc/articles/PMC7281458/ /pubmed/32403357 http://dx.doi.org/10.3390/cancers12051206 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
Bouberhan, Sara
Philp, Lauren
Hill, Sarah
Al-Alem, Linah F.
Rueda, Bo
Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer
title Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer
title_full Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer
title_fullStr Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer
title_full_unstemmed Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer
title_short Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer
title_sort exploiting the prevalence of homologous recombination deficiencies in high-grade serous ovarian cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281458/
https://www.ncbi.nlm.nih.gov/pubmed/32403357
http://dx.doi.org/10.3390/cancers12051206
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