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dc.contributor.authorSundar, R
dc.contributor.authorMiranda, S
dc.contributor.authorRodrigues, DN
dc.contributor.authorChénard-Poirier, M
dc.contributor.authorDolling, D
dc.contributor.authorClarke, M
dc.contributor.authorFigueiredo, I
dc.contributor.authorBertan, C
dc.contributor.authorYuan, W
dc.contributor.authorFerreira, A
dc.contributor.authorChistova, R
dc.contributor.authorBoysen, G
dc.contributor.authorPerez, DR
dc.contributor.authorTunariu, N
dc.contributor.authorMateo, J
dc.contributor.authorWotherspoon, A
dc.contributor.authorChau, I
dc.contributor.authorCunningham, D
dc.contributor.authorValeri, N
dc.contributor.authorCarreira, S
dc.contributor.authorde Bono, J
dc.date.accessioned2019-07-17T09:03:31Z
dc.date.issued2018-12
dc.identifier.citationClinical colorectal cancer, 2018, 17 (4), pp. 280 - 284
dc.identifier.issn1533-0028
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3290
dc.identifier.eissn1938-0674en_US
dc.identifier.doi10.1016/j.clcc.2018.05.011en_US
dc.description.abstractBackground Loss of ataxia telangiectasia mutated (ATM), a key protein regulating DNA repair signaling, has been suggested to increase sensitivity to DNA damaging agents. We conducted a study analyzing the loss of ATM protein expression in colorectal cancer and correlated this with clinical outcomes.Materials and methods The clinical outcomes data and tumor samples from metastatic colorectal cancer patients referred to the Royal Marsden Hospital Drug Development Unit (United Kingdom) from 2012 to 2016 and providing consent for a molecular characterization study were analyzed. Immunohistochemistry (IHC) slides were assessed by a pathologist for nuclear staining intensity of ATM and semiquantitatively scored. ATM loss was defined as a nuclear H-score of ≤ 10.Results Of 223 colorectal cancer samples, ATM IHC loss was identified in 17 (8%). ATM loss was independent of the RAS and RAF mutational status. ATM loss was associated with superior overall survival after first-line oxaliplatin-based therapy (49 vs. 32 months; hazard ratio [HR], 2.52) but not with irinotecan-based therapy (24 vs. 33 months; HR, 0.72). ATM loss was not prognostic for survival from the diagnosis (50 vs. 44 months; HR, 1.43).Conclusion ATM could be considered a biomarker for the development of novel DNA repair targeting agents and treatment of colorectal cancer.
dc.formatPrint-Electronic
dc.format.extent280 - 284
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectLiver Neoplasms
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectPrognosis
dc.subjectSurvival Rate
dc.subjectRetrospective Studies
dc.subjectFollow-Up Studies
dc.subjectDNA Repair
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.subjectAtaxia Telangiectasia Mutated Proteins
dc.subjectBiomarkers, Tumor
dc.subjectOxaliplatin
dc.titleAtaxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer.
dc.typeJournal Article
dcterms.dateAccepted2018-05-31
rioxxterms.versionofrecord10.1016/j.clcc.2018.05.011
rioxxterms.licenseref.startdate2018-12en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical colorectal cancer
pubs.issue4
pubs.notesNot known
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
pubs.publication-statusPublished
pubs.volume17en_US
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
dc.contributor.icrauthorDe Bono, Johannen
dc.contributor.icrauthorTunariu, Ninaen
dc.contributor.icrauthorChau, Ianen
dc.contributor.icrauthorCunningham, Daviden
dc.contributor.icrauthorValeri, Nicolaen
dc.contributor.icrauthorCarreira, Suzanneen
dc.contributor.icrauthorMiranda, Susanaen


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