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@ARTICLE{Schmidt:131608,
      author       = {C. Schmidt$^*$ and N. A. Schubert and S. Brabetz$^*$ and N.
                      Mack$^*$ and B. Schwalm$^*$ and J. A. Chan and F. Selt$^*$
                      and C. Herold-Mende and O. Witt$^*$ and T. Milde$^*$ and S.
                      Pfister$^*$ and A. Korshunov$^*$ and M. Kool$^*$},
      title        = {{P}reclinical drug screen reveals topotecan, actinomycin
                      {D}, and volasertib as potential new therapeutic candidates
                      for {ETMR} brain tumor patients.},
      journal      = {Neuro-Oncology},
      volume       = {19},
      number       = {12},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2017-06240},
      pages        = {1607 - 1617},
      year         = {2017},
      abstract     = {Embryonal tumor with multilayered rosettes (ETMR) is a rare
                      and aggressive embryonal brain tumor that solely occurs in
                      infants and young children and has only recently been
                      recognized as a separate brain tumor entity in the World
                      Health Organization classification for CNS tumors. Patients
                      have a very dismal prognosis with a median survival of 12
                      months upon diagnosis despite aggressive treatment. The aim
                      of this study was to develop novel treatment regimens in a
                      preclinical drug screen in order to inform potentially more
                      active clinical trial protocols.We have carried out an in
                      vitro and in vivo drug screen using the ETMR cell line BT183
                      and its xenograft model. Furthermore, we have generated the
                      first patient-derived xenograft (PDX) model for ETMR and
                      evaluated our top drug candidates in an in vitro drug screen
                      using this model.BT183 cells are very sensitive to the
                      topoisomerase inhibitors topotecan and doxorubicin, to the
                      epigenetic agents decitabine and panobinostat, to
                      actinomycin D, and to targeted drugs such as the polo-like
                      kinase 1 (PLK1) inhibitor volasertib, the aurora kinase A
                      inhibitor alisertib, and the mammalian target of rapamycin
                      (mTOR) inhibitor MLN0128. In xenograft mice, monotherapy
                      with topotecan, volasertib, and actinomycin D led to a
                      temporary response in tumor growth and a significant
                      increase in survival. Finally, using multi-agent treatment
                      regimens of topotecan or doxorubicin combined with
                      methotrexate and vincristine, the response in tumor growth
                      and survival was further increased compared with mice
                      receiving single treatments.We have identified several
                      promising candidates for combination therapies in future
                      clinical trials for ETMR patients.},
      cin          = {G340 / B062 / G380},
      ddc          = {610},
      cid          = {I:(DE-He78)G340-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)G380-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28482026},
      pmc          = {pmc:PMC5716199},
      doi          = {10.1093/neuonc/nox093},
      url          = {https://inrepo02.dkfz.de/record/131608},
}