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dc.contributor.authorWinkler, C
dc.contributor.authorArmenia, J
dc.contributor.authorJones, GN
dc.contributor.authorTobalina, L
dc.contributor.authorSale, MJ
dc.contributor.authorPetreus, T
dc.contributor.authorBaird, T
dc.contributor.authorSerra, V
dc.contributor.authorWang, AT
dc.contributor.authorLau, A
dc.contributor.authorGarnett, MJ
dc.contributor.authorJaaks, P
dc.contributor.authorCoker, EA
dc.contributor.authorPierce, AJ
dc.contributor.authorO'Connor, MJ
dc.contributor.authorLeo, E
dc.date.accessioned2021-04-21T09:20:10Z
dc.date.available2021-04-21T09:20:10Z
dc.identifier.citationBritish journal of cancer, 2021, 124 (5), pp. 951 - 962
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4531
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/s41416-020-01199-4
dc.description.abstractBackground Schlafen 11 (SLFN11) has been linked with response to DNA-damaging agents (DDA) and PARP inhibitors. An in-depth understanding of several aspects of its role as a biomarker in cancer is missing, as is a comprehensive analysis of the clinical significance of SLFN11 as a predictive biomarker to DDA and/or DNA damage-response inhibitor (DDRi) therapies.Methods We used a multidisciplinary effort combining specific immunohistochemistry, pharmacology tests, anticancer combination therapies and mechanistic studies to assess SLFN11 as a potential biomarker for stratification of patients treated with several DDA and/or DDRi in the preclinical and clinical setting.Results SLFN11 protein associated with both preclinical and patient treatment response to DDA, but not to non-DDA or DDRi therapies, such as WEE1 inhibitor or olaparib in breast cancer. SLFN11-low/absent cancers were identified across different tumour types tested. Combinations of DDA with DDRi targeting the replication-stress response (ATR, CHK1 and WEE1) could re-sensitise SLFN11-absent/low cancer models to the DDA treatment and were effective in upper gastrointestinal and genitourinary malignancies.Conclusion SLFN11 informs on the standard of care chemotherapy based on DDA and the effect of selected combinations with ATR, WEE1 or CHK1 inhibitor in a wide range of cancer types and models.
dc.formatPrint-Electronic
dc.format.extent951 - 962
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSLFN11 informs on standard of care and novel treatments in a wide range of cancer models.
dc.typeJournal Article
dcterms.dateAccepted2020-11-11
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41416-020-01199-4
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue5
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/Target Biology and Genomic Instability
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/Target Biology and Genomic Instability
pubs.publication-statusPublished
pubs.volume124
pubs.embargo.termsNot known
icr.researchteamTarget Biology and Genomic Instability
icr.researchteamTarget Biology and Genomic Instabilityen_US
dc.contributor.icrauthorWang, Andersonen


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0