dc.contributor.author | Winkler, C | |
dc.contributor.author | Armenia, J | |
dc.contributor.author | Jones, GN | |
dc.contributor.author | Tobalina, L | |
dc.contributor.author | Sale, MJ | |
dc.contributor.author | Petreus, T | |
dc.contributor.author | Baird, T | |
dc.contributor.author | Serra, V | |
dc.contributor.author | Wang, AT | |
dc.contributor.author | Lau, A | |
dc.contributor.author | Garnett, MJ | |
dc.contributor.author | Jaaks, P | |
dc.contributor.author | Coker, EA | |
dc.contributor.author | Pierce, AJ | |
dc.contributor.author | O'Connor, MJ | |
dc.contributor.author | Leo, E | |
dc.date.accessioned | 2021-04-21T09:20:10Z | |
dc.date.available | 2021-04-21T09:20:10Z | |
dc.date.issued | 2021-03-02 | |
dc.identifier.citation | British journal of cancer, 2021, 124 (5), pp. 951 - 962 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4531 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/s41416-020-01199-4 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 951 - 962 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGERNATURE | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | SLFN11 informs on standard of care and novel treatments in a wide range of cancer models. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-11-11 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41416-020-01199-4 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 5 | |
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/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-status | Published | |
pubs.volume | 124 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Target Biology and Genomic Instability | |
icr.researchteam | Target Biology and Genomic Instability | |
dc.contributor.icrauthor | Wang, Anderson | |