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dc.contributor.authorCastroviejo-Bermejo, Martaen
dc.contributor.authorCruz, Cristinaen
dc.contributor.authorLlop-Guevara, Albaen
dc.contributor.authorGutiérrez-Enríquez, Saraen
dc.contributor.authorDucy, Mandyen
dc.contributor.authorIbrahim, Yasir Husseinen
dc.contributor.authorGris-Oliver, Alberten
dc.contributor.authorPellegrino, Benedettaen
dc.contributor.authorBruna, Alejandraen
dc.contributor.authorGuzmán, Martaen
dc.contributor.authorRodríguez, Olgaen
dc.contributor.authorGrueso, Juditen
dc.contributor.authorBonache, Sandraen
dc.contributor.authorMoles-Fernández, Alejandroen
dc.contributor.authorVillacampa, Guillermoen
dc.contributor.authorViaplana, Cristinaen
dc.contributor.authorGómez, Patriciaen
dc.contributor.authorVidal, Mariaen
dc.contributor.authorPeg, Vicenteen
dc.contributor.authorSerres-Créixams, Xavieren
dc.contributor.authorDellaire, Grahamen
dc.contributor.authorSimard, Jacquesen
dc.contributor.authorNuciforo, Paoloen
dc.contributor.authorRubio, Isabel Ten
dc.contributor.authorDienstmann, Rodrigoen
dc.contributor.authorBarrett, J Carlen
dc.contributor.authorCaldas, Carlosen
dc.contributor.authorBaselga, Joséen
dc.contributor.authorSaura, Cristinaen
dc.contributor.authorCortés, Javieren
dc.contributor.authorDéas, Olivieren
dc.contributor.authorJonkers, Josen
dc.contributor.authorMasson, Jean-Yvesen
dc.contributor.authorCairo, Stefanoen
dc.contributor.authorJudde, Jean-Gabrielen
dc.contributor.authorO'Connor, Mark Jen
dc.contributor.authorDíez, Orlanden
dc.contributor.authorBalmaña, Judithen
dc.contributor.authorSerra, Violetaen
dc.date.accessioned2019-04-29T23:30:53Z
dc.date.available2019-04-29T23:30:53Z
dc.date.issued2018-12en
dc.identifier.issn1757-4676
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/292100
dc.description.abstractPoly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are effective in cancers with defective homologous recombination DNA repair (HRR), including BRCA1/2-related cancers. A test to identify additional HRR-deficient tumors will help to extend their use in new indications. We evaluated the activity of the PARPi olaparib in patient-derived tumor xenografts (PDXs) from breast cancer (BC) patients and investigated mechanisms of sensitivity through exome sequencing, BRCA1 promoter methylation analysis, and immunostaining of HRR proteins, including RAD51 nuclear foci. In an independent BC PDX panel, the predictive capacity of the RAD51 score and the homologous recombination deficiency (HRD) score were compared. To examine the clinical feasibility of the RAD51 assay, we scored archival breast tumor samples, including PALB2-related hereditary cancers. The RAD51 score was highly discriminative of PARPi sensitivity versus PARPi resistance in BC PDXs and outperformed the genomic test. In clinical samples, all PALB2-related tumors were classified as HRR-deficient by the RAD51 score. The functional biomarker RAD51 enables the identification of PARPi-sensitive BC and broadens the population who may benefit from this therapy beyond BRCA1/2-related cancers.
dc.format.mediumPrinten
dc.languageengen
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectBreast Neoplasmsen
dc.subjectPiperazinesen
dc.subjectPhthalazinesen
dc.subjectAntineoplastic Agentsen
dc.subjectDrug Resistance, Neoplasmen
dc.subjectFemaleen
dc.subjectRad51 Recombinaseen
dc.subjectHomologous Recombinationen
dc.subjectHeterograftsen
dc.subjectBiomarkers, Tumoren
dc.subjectPoly(ADP-ribose) Polymerase Inhibitorsen
dc.titleA RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation.en
dc.typeArticle
prism.issueIdentifier12en
prism.publicationDate2018en
prism.publicationNameEMBO molecular medicineen
prism.volume10en
dc.identifier.doi10.17863/CAM.39255
dcterms.dateAccepted2018-10-16en
rioxxterms.versionofrecord10.15252/emmm.201809172en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-12en
dc.contributor.orcidLlop-Guevara, Alba [0000-0002-7913-9472]
dc.contributor.orcidGutiérrez-Enríquez, Sara [0000-0002-1711-6101]
dc.contributor.orcidGris-Oliver, Albert [0000-0003-1802-9541]
dc.contributor.orcidPellegrino, Benedetta [0000-0001-9353-7445]
dc.contributor.orcidBruna, Alejandra [0000-0003-1214-9665]
dc.contributor.orcidPeg, Vicente [0000-0002-5203-6166]
dc.contributor.orcidSerres-Créixams, Xavier [0000-0001-8642-467X]
dc.contributor.orcidDellaire, Graham [0000-0002-3466-6316]
dc.contributor.orcidCaldas, Carlos [0000-0003-3547-1489]
dc.contributor.orcidSaura, Cristina [0000-0001-8296-5065]
dc.contributor.orcidJonkers, Jos [0000-0002-9264-9792]
dc.contributor.orcidBalmaña, Judith [0000-0002-0762-6415]
dc.contributor.orcidSerra, Violeta [0000-0001-6620-1065]
dc.identifier.eissn1757-4684
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (A3086)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (60098573)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (CB4140)
pubs.funder-project-idCancer Research UK (20544)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Research Infrastructures (RI) (731105)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International