dc.contributor.author | Williamson, CT | |
dc.contributor.author | Miller, R | |
dc.contributor.author | Pemberton, HN | |
dc.contributor.author | Jones, SE | |
dc.contributor.author | Campbell, J | |
dc.contributor.author | Konde, A | |
dc.contributor.author | Badham, N | |
dc.contributor.author | Rafiq, R | |
dc.contributor.author | Brough, R | |
dc.contributor.author | Gulati, A | |
dc.contributor.author | Ryan, CJ | |
dc.contributor.author | Francis, J | |
dc.contributor.author | Vermulen, PB | |
dc.contributor.author | Reynolds, AR | |
dc.contributor.author | Reaper, PM | |
dc.contributor.author | Pollard, JR | |
dc.contributor.author | Ashworth, A | |
dc.contributor.author | Lord, CJ | |
dc.date.accessioned | 2016-11-22T15:18:54Z | |
dc.date.issued | 2016-12-13 | |
dc.identifier.citation | Nature communications, 2016, 7 pp. 13837 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/223 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/ncomms13837 | |
dc.description.abstract | Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations in human cancer, but therapeutic approaches that target these defects are not yet clinically available. We demonstrate that defects in ARID1A sensitize tumour cells to clinical inhibitors of the DNA damage checkpoint kinase, ATR, both in vitro and in vivo. Mechanistically, ARID1A deficiency results in topoisomerase 2A and cell cycle defects, which cause an increased reliance on ATR checkpoint activity. In ARID1A mutant tumour cells, inhibition of ATR triggers premature mitotic entry, genomic instability and apoptosis. The data presented here provide the pre-clinical and mechanistic rationale for assessing ARID1A defects as a biomarker of single-agent ATR inhibitor response and represents a novel synthetic lethal approach to targeting tumour cells. | |
dc.format | Electronic | |
dc.format.extent | 13837 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Nuclear Proteins | |
dc.subject | Transcription Factors | |
dc.subject | Antineoplastic Agents | |
dc.subject | Apoptosis | |
dc.subject | RNA Interference | |
dc.subject | Cell Cycle Checkpoints | |
dc.subject | Ataxia Telangiectasia Mutated Proteins | |
dc.title | ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-11-03 | |
rioxxterms.versionofrecord | 10.1038/ncomms13837 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-12-13 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular 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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Tumour Biology | |
icr.researchteam | Gene Function | |
icr.researchteam | Sarcoma Molecular Pathology | |
dc.contributor.icrauthor | Williamson, Christopher | |
dc.contributor.icrauthor | Jones, Samuel | |
dc.contributor.icrauthor | Campbell, James | |
dc.contributor.icrauthor | Reynolds, Andrew | |
dc.contributor.icrauthor | Lord, Christopher | |