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dc.contributor.authorCastroviejo-Bermejo, M
dc.contributor.authorCruz, C
dc.contributor.authorLlop-Guevara, A
dc.contributor.authorGutiérrez-Enríquez, S
dc.contributor.authorDucy, M
dc.contributor.authorIbrahim, YH
dc.contributor.authorGris-Oliver, A
dc.contributor.authorPellegrino, B
dc.contributor.authorBruna, A
dc.contributor.authorGuzmán, M
dc.contributor.authorRodríguez, O
dc.contributor.authorGrueso, J
dc.contributor.authorBonache, S
dc.contributor.authorMoles-Fernández, A
dc.contributor.authorVillacampa, G
dc.contributor.authorViaplana, C
dc.contributor.authorGómez, P
dc.contributor.authorVidal, M
dc.contributor.authorPeg, V
dc.contributor.authorSerres-Créixams, X
dc.contributor.authorDellaire, G
dc.contributor.authorSimard, J
dc.contributor.authorNuciforo, P
dc.contributor.authorRubio, IT
dc.contributor.authorDienstmann, R
dc.contributor.authorBarrett, JC
dc.contributor.authorCaldas, C
dc.contributor.authorBaselga, J
dc.contributor.authorSaura, C
dc.contributor.authorCortés, J
dc.contributor.authorDéas, O
dc.contributor.authorJonkers, J
dc.contributor.authorMasson, J-Y
dc.contributor.authorCairo, S
dc.contributor.authorJudde, J-G
dc.contributor.authorO'Connor, MJ
dc.contributor.authorDíez, O
dc.contributor.authorBalmaña, J
dc.contributor.authorSerra, V
dc.coverage.spatialEngland
dc.date.accessioned2022-09-01T14:44:47Z
dc.date.available2022-09-01T14:44:47Z
dc.date.issued2018-12-01
dc.identifierARTN e9172
dc.identifieremmm.201809172
dc.identifier.citationEMBO Molecular Medicine, 2018, 10 (12), pp. e9172 -en_US
dc.identifier.issn1757-4676
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5366
dc.identifier.eissn1757-4684
dc.identifier.eissn1757-4684
dc.identifier.doi10.15252/emmm.201809172
dc.identifier.doi10.15252/emmm.201809172
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.formatPrint
dc.format.extente9172 -
dc.languageeng
dc.language.isoengen_US
dc.publisherWILEYen_US
dc.relation.ispartofEMBO Molecular Medicine
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectBRCA1
dc.subjectPALB2
dc.subjectPARP inhibitors
dc.subjectRAD51
dc.subjecthomologous recombination
dc.subjectAnimals
dc.subjectAntineoplastic Agents
dc.subjectBiomarkers, Tumor
dc.subjectBreast Neoplasms
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.subjectHeterografts
dc.subjectHomologous Recombination
dc.subjectHumans
dc.subjectMice
dc.subjectPhthalazines
dc.subjectPiperazines
dc.subjectPoly(ADP-ribose) Polymerase Inhibitors
dc.subjectRad51 Recombinase
dc.titleA RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-12-01
dc.date.updated2022-09-01T14:43:57Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.15252/emmm.201809172en_US
rioxxterms.licenseref.startdate2018-12-01
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30377213
pubs.issue12
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Preclinical Modelling of Paediatric Cancer Evolution
pubs.publication-statusPublished
pubs.publisher-urlhttp://dx.doi.org/10.15252/emmm.201809172
pubs.volume10
icr.researchteamPreclin Paed Cancer Evoen_US
dc.contributor.icrauthorBruna Cabot, Alejandra
icr.provenanceDeposited by Mr Arek Surman on 2022-09-01. Deposit type is initial. No. of files: 1. Files: A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation. .pdf


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