dc.contributor.author | Miller, RE | |
dc.contributor.author | Brough, R | |
dc.contributor.author | Bajrami, I | |
dc.contributor.author | Williamson, CT | |
dc.contributor.author | McDade, S | |
dc.contributor.author | Campbell, J | |
dc.contributor.author | Kigozi, A | |
dc.contributor.author | Rafiq, R | |
dc.contributor.author | Pemberton, H | |
dc.contributor.author | Natrajan, R | |
dc.contributor.author | Joel, J | |
dc.contributor.author | Astley, H | |
dc.contributor.author | Mahoney, C | |
dc.contributor.author | Moore, JD | |
dc.contributor.author | Torrance, C | |
dc.contributor.author | Gordan, JD | |
dc.contributor.author | Webber, JT | |
dc.contributor.author | Levin, RS | |
dc.contributor.author | Shokat, KM | |
dc.contributor.author | Bandyopadhyay, S | |
dc.contributor.author | Lord, CJ | |
dc.contributor.author | Ashworth, A | |
dc.date.accessioned | 2017-03-06T15:44:40Z | |
dc.date.issued | 2016-07-01 | |
dc.identifier.citation | Molecular cancer therapeutics, 2016, 15 (7), pp. 1472 - 1484 | |
dc.identifier.issn | 1535-7163 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/474 | |
dc.identifier.eissn | 1538-8514 | |
dc.identifier.doi | 10.1158/1535-7163.mct-15-0554 | |
dc.description.abstract | New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G1-S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. Mol Cancer Ther; 15(7); 1472-84. ©2016 AACR. | |
dc.format | Print-Electronic | |
dc.format.extent | 1472 - 1484 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Adenocarcinoma, Clear Cell | |
dc.subject | Ovarian Neoplasms | |
dc.subject | Disease Models, Animal | |
dc.subject | Retinoblastoma Protein | |
dc.subject | Nuclear Proteins | |
dc.subject | Transcription Factors | |
dc.subject | Antineoplastic Agents | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Drug Screening Assays, Antitumor | |
dc.subject | Drug Evaluation, Preclinical | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Gene Expression Profiling | |
dc.subject | Apoptosis | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Female | |
dc.subject | Proto-Oncogene Proteins p21(ras) | |
dc.subject | Molecular Targeted Therapy | |
dc.subject | Dasatinib | |
dc.subject | Synthetic Lethal Mutations | |
dc.title | Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-04-06 | |
rioxxterms.versionofrecord | 10.1158/1535-7163.mct-15-0554 | |
rioxxterms.licenseref.startdate | 2016-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular cancer therapeutics | |
pubs.issue | 7 | |
pubs.notes | No embargo | |
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/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
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/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
pubs.publication-status | Published | |
pubs.volume | 15 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Functional Genomics | |
icr.researchteam | Gene Function | |
dc.contributor.icrauthor | Campbell, James | |
dc.contributor.icrauthor | Natrajan, Rachael | |
dc.contributor.icrauthor | Lord, Christopher | |