RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer

Biomarker predictive; Chemotherapy; Ovarian cancer

Detalles Bibliográficos
Autores: Compadre, Amanda, van Biljon, Lillian, Valentine, Mark, Graham, Emily, Fashemi, Bisiayo, Herencia Ropero, Andrea, Llop-Guevara, Alba, Serra, Violeta
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
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:11351/10080
Acceso en línea:https://hdl.handle.net/11351/10080
http://hdl.handle.net/11351/10080
Access Level:acceso abierto
Palabra clave:Ovaris - Càncer - Tractament
Marcadors tumorals
CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
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oai_identifier_str oai:recercat.cat:11351/10080
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
title RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
spellingShingle RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
Compadre, Amanda
Ovaris - Càncer - Tractament
Marcadors tumorals
CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
title_short RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
title_full RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
title_fullStr RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
title_full_unstemmed RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
title_sort RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
dc.creator.none.fl_str_mv Compadre, Amanda
van Biljon, Lillian
Valentine, Mark
Graham, Emily
Fashemi, Bisiayo
Herencia Ropero, Andrea
Llop-Guevara, Alba
Serra, Violeta
author Compadre, Amanda
author_facet Compadre, Amanda
van Biljon, Lillian
Valentine, Mark
Graham, Emily
Fashemi, Bisiayo
Herencia Ropero, Andrea
Llop-Guevara, Alba
Serra, Violeta
author_role author
author2 van Biljon, Lillian
Valentine, Mark
Graham, Emily
Fashemi, Bisiayo
Herencia Ropero, Andrea
Llop-Guevara, Alba
Serra, Violeta
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Compadre AJ, van Biljon LN, Valentine MC, Graham E, Fashemi B] Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St Louis, Missouri. [Llop-Guevara A, Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Herencia-Ropero A] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Ovaris - Càncer - Tractament
Marcadors tumorals
CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
topic Ovaris - Càncer - Tractament
Marcadors tumorals
CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
description Biomarker predictive; Chemotherapy; Ovarian cancer
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
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/11351/10080
http://hdl.handle.net/11351/10080
url https://hdl.handle.net/11351/10080
http://hdl.handle.net/11351/10080
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Clinical Cancer Research;29(13)
https://doi.org/10.1158/1078-0432.CCR-22-3335
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
dc.source.none.fl_str_mv Scientia
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
_version_ 1869408118432071680
spelling RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian CancerCompadre, Amandavan Biljon, LillianValentine, MarkGraham, EmilyFashemi, BisiayoHerencia Ropero, AndreaLlop-Guevara, AlbaSerra, VioletaOvaris - Càncer - TractamentMarcadors tumoralsCHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, TumorDISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian NeoplasmsOther subheadings::Other subheadings::Other subheadings::/drug therapyCOMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumoralesENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricasOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaBiomarker predictive; Chemotherapy; Ovarian cancerBiomarcador predictiu; Quimioteràpia; Càncer d'ovariBiomarcador predictivo; Quimioterapia; Cáncer de ovarioPurpose: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. Experimental Design: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. Results: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78–1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33–0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25–0.75; P = 0.003) than RAD51-High status. Conclusions: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.This work was supported by the following entities: M. Mullen reports funding from the Reproductive Scientist Development Program (RSDP) supported by the Gynecologic Oncology Group Foundation, Washington University School of Medicine Division of Physician Scientists Dean's Scholar Program, and grant 2021265 from the Doris Duke Charitable Foundation through the COVID-19 Fund to Retain Clinical Scientists collaborative grant program. D. Khabele reports funding from RO1CA243511, University of Kansas Cancer Center P30 CA168524. D.G. Mutch reports funding from Washington University School of Medicine grant 5U1-CA180860–04.American Association for Cancer ResearchInstitut Català de la Salut[Compadre AJ, van Biljon LN, Valentine MC, Graham E, Fashemi B] Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St Louis, Missouri. [Llop-Guevara A, Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Herencia-Ropero A] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, SpainVall d'Hebron Barcelona Hospital Campus202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/10080http://hdl.handle.net/11351/10080Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésClinical Cancer Research;29(13)https://doi.org/10.1158/1078-0432.CCR-22-3335Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/100802026-05-29T05:05:01Z
score 15,811543

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