Translational research opportunities regarding homologous recombination in ovarian cancer

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 ruca...

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Autores: Romeo, Margarita, Pardo, Juan Carlos, Martínez Cardús, Anna, Martínez Balibrea, Eva, Quiroga Garcia, Vanesa, Martínez-Román, Sergio, Solé, Francesc, Margelí, Mireia, Mesía Nin, Ricard
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/215715
Acceso en línea:https://hdl.handle.net/2445/215715
Access Level:acceso abierto
Palabra clave:Assaigs clínics
Medicaments antineoplàstics
Càncer d'ovari
Clinical trials
Antineoplastic agents
Ovarian cancer
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repository_id_str
spelling Translational research opportunities regarding homologous recombination in ovarian cancerRomeo, MargaritaPardo, Juan CarlosMartínez Cardús, AnnaMartínez Balibrea, EvaQuiroga Garcia, VanesaMartínez-Román, SergioSolé, FrancescMargelí, MireiaMesía Nin, RicardAssaigs clínicsMedicaments antineoplàsticsCàncer d'ovariClinical trialsAntineoplastic agentsOvarian cancerHomologous 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. Keywords: BRCA1; BRCA2; PARP inhibitors; deficient homologous recombination; high-grade serous ovarian cancer; mechanisms of resistance; ovarian cancer.MDPI2024202420182024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfhttps://hdl.handle.net/2445/215715Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/ijms19103249International Journal of Molecular Sciences, 2018, vol. 19, num.10https://doi.org/10.3390/ijms19103249cc-by (c) Romeo, M. et al., 2018http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2157152026-05-29T05:05:01Z
dc.title.none.fl_str_mv Translational research opportunities regarding homologous recombination in ovarian cancer
title Translational research opportunities regarding homologous recombination in ovarian cancer
spellingShingle Translational research opportunities regarding homologous recombination in ovarian cancer
Romeo, Margarita
Assaigs clínics
Medicaments antineoplàstics
Càncer d'ovari
Clinical trials
Antineoplastic agents
Ovarian cancer
title_short Translational research opportunities regarding homologous recombination in ovarian cancer
title_full Translational research opportunities regarding homologous recombination in ovarian cancer
title_fullStr Translational research opportunities regarding homologous recombination in ovarian cancer
title_full_unstemmed Translational research opportunities regarding homologous recombination in ovarian cancer
title_sort Translational research opportunities regarding homologous recombination in ovarian cancer
dc.creator.none.fl_str_mv Romeo, Margarita
Pardo, Juan Carlos
Martínez Cardús, Anna
Martínez Balibrea, Eva
Quiroga Garcia, Vanesa
Martínez-Román, Sergio
Solé, Francesc
Margelí, Mireia
Mesía Nin, Ricard
author Romeo, Margarita
author_facet Romeo, Margarita
Pardo, Juan Carlos
Martínez Cardús, Anna
Martínez Balibrea, Eva
Quiroga Garcia, Vanesa
Martínez-Román, Sergio
Solé, Francesc
Margelí, Mireia
Mesía Nin, Ricard
author_role author
author2 Pardo, Juan Carlos
Martínez Cardús, Anna
Martínez Balibrea, Eva
Quiroga Garcia, Vanesa
Martínez-Román, Sergio
Solé, Francesc
Margelí, Mireia
Mesía Nin, Ricard
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Assaigs clínics
Medicaments antineoplàstics
Càncer d'ovari
Clinical trials
Antineoplastic agents
Ovarian cancer
topic Assaigs clínics
Medicaments antineoplàstics
Càncer d'ovari
Clinical trials
Antineoplastic agents
Ovarian cancer
description 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. Keywords: BRCA1; BRCA2; PARP inhibitors; deficient homologous recombination; high-grade serous ovarian cancer; mechanisms of resistance; ovarian cancer.
publishDate 2018
dc.date.none.fl_str_mv 2018
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/215715
url https://hdl.handle.net/2445/215715
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms19103249
International Journal of Molecular Sciences, 2018, vol. 19, num.10
https://doi.org/10.3390/ijms19103249
dc.rights.none.fl_str_mv cc-by (c) Romeo, M. et al., 2018
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Romeo, M. et al., 2018
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 18 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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