Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors

Inhibidors de la PARP; Metabolisme del càncer; Metformina

Detalhes bibliográficos
Autores: Lahiguera, Álvaro, Hyroššová, Petra, Figueras, Agnès, Garzón, Diana, Moreno, Roger, Soto-Cerrato, Vanessa, Serra Elizalde, Violeta
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Departament de Salut de la Generalitat de Catalunya (DS)
Repositorio:Scientia. Dipòsit d'Informació Digital del Departament de Salut
OAI Identifier:oai:scientiasalut.gencat.cat:11351/6283
Acesso em linha:https://hdl.handle.net/11351/6283
Access Level:acceso abierto
Palavra-chave:Ovaris - Càncer
Medicaments antineoplàstics - Ús terapèutic
Recombinació genètica
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga
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oai_identifier_str oai:scientiasalut.gencat.cat:11351/6283
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
title Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
spellingShingle Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
Lahiguera, Álvaro
Ovaris - Càncer
Medicaments antineoplàstics - Ús terapèutic
Recombinació genètica
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga
title_short Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
title_full Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
title_fullStr Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
title_full_unstemmed Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
title_sort Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
dc.creator.none.fl_str_mv Lahiguera, Álvaro
Hyroššová, Petra
Figueras, Agnès
Garzón, Diana
Moreno, Roger
Soto-Cerrato, Vanessa
Serra Elizalde, Violeta
author Lahiguera, Álvaro
author_facet Lahiguera, Álvaro
Hyroššová, Petra
Figueras, Agnès
Garzón, Diana
Moreno, Roger
Soto-Cerrato, Vanessa
Serra Elizalde, Violeta
author_role author
author2 Hyroššová, Petra
Figueras, Agnès
Garzón, Diana
Moreno, Roger
Soto-Cerrato, Vanessa
Serra Elizalde, Violeta
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Lahiguera Á, Figueras A, Garzón D, Moreno R] Program Against Cancer Therapeutic Resistance (ProCURE), Institut Català d'Oncologia, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain. Oncobell Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. [Hyroššová P] Departament de Ciències Fisiològiques, Universitat de Barcelona, Barcelona, Spain. [Soto-Cerrato V] Departament de Patologia i Terapèutica Experimental, Universitat de Barcelona, Barcelona, Spain. [Serra V] Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Ovaris - Càncer
Medicaments antineoplàstics - Ús terapèutic
Recombinació genètica
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga
topic Ovaris - Càncer
Medicaments antineoplàstics - Ús terapèutic
Recombinació genètica
DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga
description Inhibidors de la PARP; Metabolisme del càncer; Metformina
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
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/11351/6283
url https://hdl.handle.net/11351/6283
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv EMBO Molecular Medicine;12
https://doi.org/10.15252/emmm.201911217
info:eu-repo/grantAgreement/ES/PE2013-2016/SAF2017-85869-R
info:eu-repo/grantAgreement/ES/PE2013-2016/BFU2015-66030-R
info:eu-repo/grantAgreement/ES/PE2013-2016/PI15%2F00854
info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F01898
info:eu-repo/grantAgreement/ES/PERIS2016-2020/2017SGR449
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Scientia
reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname:Departament de Salut de la Generalitat de Catalunya (DS)
instname_str Departament de Salut de la Generalitat de Catalunya (DS)
reponame_str Scientia. Dipòsit d'Informació Digital del Departament de Salut
collection Scientia. Dipòsit d'Informació Digital del Departament de Salut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitorsLahiguera, ÁlvaroHyroššová, PetraFigueras, AgnèsGarzón, DianaMoreno, RogerSoto-Cerrato, VanessaSerra Elizalde, VioletaOvaris - CàncerMedicaments antineoplàstics - Ús terapèuticRecombinació genèticaDISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian NeoplasmsOther subheadings::Other subheadings::Other subheadings::/drug therapyPHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous RecombinationENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricasOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaFENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homólogaInhibidors de la PARP; Metabolisme del càncer; MetforminaInhibidores de PARP, Metabolismo del cáncer; MetforminaPARP inhibitors; Cancer metabolism; MetforminMitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. How genomic instability influences the metabolic capacity of cancer cells is nevertheless poorly understood. Here, we show that homologous recombination-defective (HRD) cancers rely on oxidative metabolism to supply NAD+ and ATP for poly(ADP-ribose) polymerase (PARP)-dependent DNA repair mechanisms. Studies in breast and ovarian cancer HRD models depict a metabolic shift that includes enhanced expression of the oxidative phosphorylation (OXPHOS) pathway and its key components and a decline in the glycolytic Warburg phenotype. Hence, HRD cells are more sensitive to metformin and NAD+ concentration changes. On the other hand, shifting from an OXPHOS to a highly glycolytic metabolism interferes with the sensitivity to PARP inhibitors (PARPi) in these HRD cells. This feature is associated with a weak response to PARP inhibition in patient-derived xenografts, emerging as a new mechanism to determine PARPi sensitivity. This study shows a mechanistic link between two major cancer hallmarks, which in turn suggests novel possibilities for specifically treating HRD cancers with OXPHOS inhibitors.This study has been funded by the Ministerio de Ciencia, Innovación y Universidades, which is part of the Agencia Estatal de Investigación (AEI), through the project SAF2017-85869-R (cofunded by the European Regional Development Fund (ERDF), a way to build Europe) to FV and BFU2015-66030-R to JCP; by the FIS PI15/00854 and FIS PI16/01898 (Instituto Carlos III, cofunded by FEDER funds/European Regional Development Fund (ERDF), a way to build Europe) to MAP and AVillanueva and with the support of the Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia (2017SGR449) to FV. We thank the CERCA Program/Generalitat de Catalunya for their institutional support. We particularly wish to acknowledge the collaboration of the patients and the IDIBGI Biobank (Biobanc IDIBGI, B.0000872), which is part of the Spanish National Biobank Network and the Xarxa de Bancs de Tumors de Catalunya (XBTC), financed by the Pla Director d'Oncologia de Catalunya, Spain. We thank Cristina Saura (Breast Cancer & Melanoma Group) and people from the Experimental Therapeutics Group at VHIO and Sara González (Unitat de Diagnòstic Molecular, ICO-Duran i Reynals). We thank H. Simon, R. Bartrons, and A. Manzano (Universitat de Barcelona) and A. Vaquero (IDIBELL) for reagents.WileyInstitut Català de la Salut[Lahiguera Á, Figueras A, Garzón D, Moreno R] Program Against Cancer Therapeutic Resistance (ProCURE), Institut Català d'Oncologia, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain. Oncobell Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. [Hyroššová P] Departament de Ciències Fisiològiques, Universitat de Barcelona, Barcelona, Spain. [Soto-Cerrato V] Departament de Patologia i Terapèutica Experimental, Universitat de Barcelona, Barcelona, Spain. [Serra V] Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC, Instituto de Salud Carlos III, Madrid, SpainVall d'Hebron Barcelona Hospital Campus202120212020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/6283Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésEMBO Molecular Medicine;12https://doi.org/10.15252/emmm.201911217info:eu-repo/grantAgreement/ES/PE2013-2016/SAF2017-85869-Rinfo:eu-repo/grantAgreement/ES/PE2013-2016/BFU2015-66030-Rinfo:eu-repo/grantAgreement/ES/PE2013-2016/PI15%2F00854info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F01898info:eu-repo/grantAgreement/ES/PERIS2016-2020/2017SGR449Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/62832026-06-12T09:38:37Z
score 15,81155

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