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DC Field | Value | Language |
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dc.contributor.author | Wilkerson, PM | - |
dc.contributor.author | Dedes, KJ | - |
dc.contributor.author | Samartzis, EP | - |
dc.contributor.author | Dedes, I | - |
dc.contributor.author | Lambros, MB | - |
dc.contributor.author | Natrajan, R | - |
dc.contributor.author | Gauthier, A | - |
dc.contributor.author | Piscuoglio, S | - |
dc.contributor.author | Töpfer, C | - |
dc.contributor.author | Vukovic, V | - |
dc.contributor.author | Daley, F | - |
dc.contributor.author | Weigelt, B | - |
dc.contributor.author | Reis-Filho, JS | - |
dc.date.accessioned | 2017-08-15T08:40:27Z | - |
dc.date.available | 2017-01-01 | - |
dc.date.available | 2017-08-15T08:40:27Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Oncotarget, 2017, 8 (4), pp. 6057 - 6066 | en_US |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/15020 | - |
dc.description.abstract | Purpose: To determine if models of ovarian clear cell carcinomas (OCCCs) harbouring defects in homologous recombination (HR) DNA repair of double strand breaks (DSBs) are sensitive to cisplatin and/or PARP inhibition. Experimental Design: The HR status of 12 OCCC cell lines was determined using RAD51/γH2AX foci formation assays. Sensitivity to cisplatin and the PARP inhibitor BMN-673 was correlated with HR status. BRCA1, BRCA2, MRE11 and PTEN loss of expression was investigated as a potential determinant of BMN-673 sensitivity. A tissue microarray containing 50 consecutive primary OCCC was assessed for PTEN expression using immunohistochemistry. Results: A subset of OCCC cells displayed reduced RAD51 foci formation in the presence of DNA DSBs, suggestive of HR defects. HR-defective OCCC cells, with the exception of KOC-7c, had higher sensitivity to cisplatin/ BMN-673 than HR-competent OCCC cell lines (Log10 SF50 -9.4 (SD +/- 0.29) vs -8.1 (SD +/- 0.35), mean difference 1.3, p < 0.01). Of the cell lines studied, two, TOV-21G and KOC-7c, showed loss of PTEN expression. In primary OCCCs, loss of PTEN expression was observed in 10% (5/49) of cases. Conclusions: A subset of OCCC cells are sensitive to PARP inhibition in vitro, which can be predicted by HR defects as defined by γH2AX/RAD51 foci formation. These results provide a rationale for the testing of HR deficiency and PARP inhibitors as a targeted therapy in a subset of OCCCs. | en_US |
dc.format.extent | 6057 - 6066 | - |
dc.language.iso | en | en_US |
dc.title | Preclinical evaluation of the PARP inhibitor BMN-673 for the treatment of ovarian clear cell cancer | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.18632/oncotarget.14011 | - |
dc.relation.isPartOf | Oncotarget | - |
pubs.issue | 4 | - |
pubs.publication-status | Published | - |
pubs.volume | 8 | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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File | Description | Size | Format | |
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FullText.pdf | 1.93 MB | Adobe PDF | View/Open |
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