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dc.contributor.authorNi, Jingen_US
dc.contributor.authorRamkissoon, Shakti H.en_US
dc.contributor.authorXie, Shaozhenen_US
dc.contributor.authorGoel, Shomen_US
dc.contributor.authorStover, Daniel G.en_US
dc.contributor.authorGuo, Hanbingen_US
dc.contributor.authorLuu, Victoren_US
dc.contributor.authorMarco, Eugenioen_US
dc.contributor.authorRamkissoon, Lori A.en_US
dc.contributor.authorKang, Yun Jeeen_US
dc.contributor.authorHayashi, Marikaen_US
dc.contributor.authorNguyen, Quang-Deen_US
dc.contributor.authorLigon, Azra H.en_US
dc.contributor.authorDu, Roseen_US
dc.contributor.authorClaus, Elizabeth B.en_US
dc.contributor.authorAlexander, Brian M.en_US
dc.contributor.authorYuan, Guo-Chengen_US
dc.contributor.authorWang, Zhigang C.en_US
dc.contributor.authorIglehart, J. Dirken_US
dc.contributor.authorKrop, Ian E.en_US
dc.contributor.authorRoberts, Thomas M.en_US
dc.contributor.authorWiner, Eric P.en_US
dc.contributor.authorLin, Nancy U.en_US
dc.contributor.authorLigon, Keith L.en_US
dc.contributor.authorZhao, Jean J.en_US
dc.date.accessioned2017-01-03T23:48:54Z
dc.date.issued2016en_US
dc.identifier.citationNi, J., S. H. Ramkissoon, S. Xie, S. Goel, D. G. Stover, H. Guo, V. Luu, et al. 2016. “Combination inhibition of PI3K and mTORC1 yields durable remissions in orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases.” Nature medicine 22 (7): 723-726. doi:10.1038/nm.4120. http://dx.doi.org/10.1038/nm.4120.en
dc.identifier.issn1078-8956en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29739008
dc.description.abstractBrain metastases represent the greatest clinical challenge in treating HER2-positive breast cancer. We report the development of orthotopic patient-derived xenografts (PDXs) of HER2-expressing breast cancer brain metastases (BCBM), and their use for the identification of targeted combination therapies. Combined inhibition of PI3K and mTOR resulted in durable tumor regressions in three of five PDXs, and therapeutic response correlated with reduction of 4EBP1 phosphorylation. The two non-responding PDXs showed hypermutated genomes with enrichment of mutations in DNA repair genes, suggesting an association of genomic instability with therapeutic resistance. These findings suggest that a biomarker-driven clinical trial of PI3K inhibitor plus an mTOR inhibitor should be conducted for patients with HER2-positive BCBM.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nm.4120en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938731/pdf/en
dash.licenseLAAen_US
dc.titleCombination inhibition of PI3K and mTORC1 yields durable remissions in orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastasesen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature medicineen
dash.depositing.authorNi, Jingen_US
dc.date.available2017-01-03T23:48:54Z
dc.identifier.doi10.1038/nm.4120*
dash.authorsorderedfalse
dash.contributor.affiliatedXie, Shaozhen
dash.contributor.affiliatedGoel, Shom
dash.contributor.affiliatedStover, Daniel G.
dash.contributor.affiliatedRoberts, Thomas
dash.contributor.affiliatedNi, Jing
dash.contributor.affiliatedLin, Nancy
dash.contributor.affiliatedZhao, Jean
dash.contributor.affiliatedClaus, Elizabeth
dash.contributor.affiliatedWiner, Eric
dash.contributor.affiliatedDu, Rose
dash.contributor.affiliatedKrop, Ian
dash.contributor.affiliatedWang, Zhigang C.
dash.contributor.affiliatedAlexander, Brian
dash.contributor.affiliatedLigon, Keith
dash.contributor.affiliatedLigon, Azra


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