dc.contributor.author | Sundar, R | |
dc.contributor.author | Miranda, S | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Chénard-Poirier, M | |
dc.contributor.author | Dolling, D | |
dc.contributor.author | Clarke, M | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Bertan, C | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Ferreira, A | |
dc.contributor.author | Chistova, R | |
dc.contributor.author | Boysen, G | |
dc.contributor.author | Perez, DR | |
dc.contributor.author | Tunariu, N | |
dc.contributor.author | Mateo, J | |
dc.contributor.author | Wotherspoon, A | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Valeri, N | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | de Bono, J | |
dc.date.accessioned | 2019-07-17T09:03:31Z | |
dc.date.issued | 2018-12-01 | |
dc.identifier.citation | Clinical colorectal cancer, 2018, 17 (4), pp. 280 - 284 | |
dc.identifier.issn | 1533-0028 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3290 | |
dc.identifier.eissn | 1938-0674 | |
dc.identifier.doi | 10.1016/j.clcc.2018.05.011 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 280 - 284 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CIG MEDIA GROUP, LP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Liver Neoplasms | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Prognosis | |
dc.subject | Survival Rate | |
dc.subject | Retrospective Studies | |
dc.subject | Follow-Up Studies | |
dc.subject | DNA Repair | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Young Adult | |
dc.subject | Ataxia Telangiectasia Mutated Proteins | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Oxaliplatin | |
dc.title | Ataxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-05-31 | |
rioxxterms.versionofrecord | 10.1016/j.clcc.2018.05.011 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-12 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical colorectal cancer | |
pubs.issue | 4 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 17 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Medicine (RMH Smith Cunningham) | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
icr.researchteam | Gastrointestinal Cancer Biology and Genomics | |
dc.contributor.icrauthor | Miranda, Susana | |
dc.contributor.icrauthor | Clarke, Matthew | |
dc.contributor.icrauthor | Valeri, Nicola | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | De Bono, Johann | |