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dc.contributor.authorMalla, SB
dc.contributor.authorFisher, DJ
dc.contributor.authorDomingo, E
dc.contributor.authorBlake, A
dc.contributor.authorHassanieh, S
dc.contributor.authorRedmond, KL
dc.contributor.authorRichman, SD
dc.contributor.authorYoudell, M
dc.contributor.authorWalker, SM
dc.contributor.authorLogan, GE
dc.contributor.authorChatzipli, A
dc.contributor.authorAmirkhah, R
dc.contributor.authorHumphries, MP
dc.contributor.authorCraig, SG
dc.contributor.authorMcDermott, U
dc.contributor.authorSeymour, MT
dc.contributor.authorMorton, DG
dc.contributor.authorQuirke, P
dc.contributor.authorWest, NP
dc.contributor.authorSalto-Tellez, M
dc.contributor.authorKennedy, RD
dc.contributor.authorJohnston, PG
dc.contributor.authorTomlinson, I
dc.contributor.authorKoelzer, VH
dc.contributor.authorCampo, L
dc.contributor.authorKaplan, RS
dc.contributor.authorLongley, DB
dc.contributor.authorLawler, M
dc.contributor.authorMaughan, TS
dc.contributor.authorBrown, LC
dc.contributor.authorDunne, PD
dc.contributor.authorS:CORT consortium
dc.date.accessioned2020-11-04T12:15:21Z
dc.date.issued2021-01
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2021, 27 (1), pp. 288 - 300
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4215
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-20-3237
dc.description.abstractPurpose The DNA damage immune response (DDIR) assay was developed in breast cancer based on biology associated with deficiencies in homologous recombination and Fanconi anemia pathways. A positive DDIR call identifies patients likely to respond to platinum-based chemotherapies in breast and esophageal cancers. In colorectal cancer, there is currently no biomarker to predict response to oxaliplatin. We tested the ability of the DDIR assay to predict response to oxaliplatin-based chemotherapy in colorectal cancer and characterized the biology in DDIR-positive colorectal cancer.Experimental design Samples and clinical data were assessed according to DDIR status from patients who received either 5-fluorouracil (5-FU) or 5FUFA (bolus and infusion 5-FU with folinic acid) plus oxaliplatin (FOLFOX) within the FOCUS trial ( n = 361, stage IV), or neoadjuvant FOLFOX in the FOxTROT trial ( n = 97, stage II/III). Whole transcriptome, mutation, and IHC data of these samples were used to interrogate the biology of DDIR in colorectal cancer.Results Contrary to our hypothesis, DDIR-negative patients displayed a trend toward improved outcome for oxaliplatin-based chemotherapy compared with DDIR-positive patients. DDIR positivity was associated with microsatellite instability (MSI) and colorectal molecular subtype 1. Refinement of the DDIR signature, based on overlapping IFN-related chemokine signaling associated with DDIR positivity across colorectal cancer and breast cancer cohorts, further confirmed that the DDIR assay did not have predictive value for oxaliplatin-based chemotherapy in colorectal cancer.Conclusions DDIR positivity does not predict improved response following oxaliplatin treatment in colorectal cancer. However, data presented here suggest the potential of the DDIR assay in identifying immune-rich tumors that may benefit from immune checkpoint blockade, beyond current use of MSI status.
dc.formatPrint-Electronic
dc.format.extent288 - 300
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectS:CORT consortium
dc.titleIn-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer.
dc.typeJournal Article
dcterms.dateAccepted2020-10-01
rioxxterms.versionofrecord10.1158/1078-0432.ccr-20-3237
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue1
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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
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/Integrated Pathology
pubs.publication-statusPublished
pubs.volume27
pubs.embargo.termsNot known
icr.researchteamIntegrated Pathologyen_US
dc.contributor.icrauthorSalto-Tellez, Manuelen


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