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dc.contributor.authorWang, Dongen_US
dc.contributor.authorWang, Minen_US
dc.contributor.authorJiang, Nanen_US
dc.contributor.authorZhang, Yuanen_US
dc.contributor.authorBian, Xingen_US
dc.contributor.authorWang, Xiaoqingen_US
dc.contributor.authorRoberts, Thomas M.en_US
dc.contributor.authorZhao, Jean J.en_US
dc.contributor.authorLiu, Pixuen_US
dc.contributor.authorCheng, Hailingen_US
dc.date.accessioned2016-08-09T14:52:10Z
dc.date.issued2016en_US
dc.identifier.citationWang, Dong, Min Wang, Nan Jiang, Yuan Zhang, Xing Bian, Xiaoqing Wang, Thomas M. Roberts, Jean J. Zhao, Pixu Liu, and Hailing Cheng. 2016. “Effective use of PI3K inhibitor BKM120 and PARP inhibitor Olaparib to treat PIK3CA mutant ovarian cancer.” Oncotarget 7 (11): 13153-13166. doi:10.18632/oncotarget.7549. http://dx.doi.org/10.18632/oncotarget.7549.en
dc.identifier.issn1949-2553en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27822086
dc.description.abstractRecent preclinical studies revealed the efficacy of combined use of PI3K inhibitor BKM120 and PARP inhibitor Olaparib in breast and prostate cancers. The current study investigated the effect of such drug combination on ovarian cancer. Here we showed that combined inhibition of PI3K and PARP effectively synergized to inhibit proliferation, survival and invasion in the majority of ovarian cancer cell lines harboring PIK3CA mutations, including SKOV3, HEYA8, and IGROV1. Mechanistically, combined treatment of PARP and PI3K inhibitors resulted in an exacerbated DNA damage response and more substantially reduced AKT/mTOR signaling when compared to single-agent. Notably, ovarian cancer cells responsive to the PI3K/PARP combination displayed decreased BRCA1/2 expression upon drug treatment. Furthermore, the effect of the drug combination was corroborated in an intraperitoneal dissemination xenograft mouse model in which SKOV3 ovarian cancer cells responded with significantly decreased BRCA1 expression, suppressed PI3K/AKT signaling and reduced tumor burden. Collectively, our data suggested that combined inhibition of PI3K and PARP may be an effective therapeutic strategy for ovarian cancers with PIK3CA mutations and that the accompanied BRCA downregulation following PI3K inhibition could serve as a biomarker for the effective response to PARP inhibition.en
dc.language.isoen_USen
dc.publisherImpact Journals LLCen
dc.relation.isversionofdoi:10.18632/oncotarget.7549en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914348/pdf/en
dash.licenseLAAen_US
dc.subjectovarian canceren
dc.subjectBKM120en
dc.subjectOlapariben
dc.subjectBRCAen
dc.subjectcombination therapyen
dc.titleEffective use of PI3K inhibitor BKM120 and PARP inhibitor Olaparib to treat PIK3CA mutant ovarian canceren
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalOncotargeten
dash.depositing.authorRoberts, Thomas M.en_US
dc.date.available2016-08-09T14:52:10Z
dc.identifier.doi10.18632/oncotarget.7549*
dash.authorsorderedfalse
dash.contributor.affiliatedZhao, Jean
dash.contributor.affiliatedRoberts, Thomas


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