PMID- 28482026
OWN - NLM
STAT- MEDLINE
DCOM- 20180814
LR  - 20220316
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 19
IP  - 12
DP  - 2017 Nov 29
TI  - Preclinical drug screen reveals topotecan, actinomycin D, and volasertib as 
      potential new therapeutic candidates for ETMR brain tumor patients.
PG  - 1607-1617
LID - 10.1093/neuonc/nox093 [doi]
AB  - BACKGROUND: 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. METHODS: 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. 
      RESULTS: 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. CONCLUSIONS: We have identified 
      several promising candidates for combination therapies in future clinical trials 
      for ETMR patients.
CI  - (c) The Author(s) 2017. Published by Oxford University Press on behalf of the 
      Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com
FAU - Schmidt, Christin
AU  - Schmidt C
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Schubert, Nil A
AU  - Schubert NA
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Brabetz, Sebastian
AU  - Brabetz S
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Mack, Norman
AU  - Mack N
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Schwalm, Benjamin
AU  - Schwalm B
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Chan, Jennifer A
AU  - Chan JA
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Selt, Florian
AU  - Selt F
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Herold-Mende, Christel
AU  - Herold-Mende C
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Witt, Olaf
AU  - Witt O
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Milde, Till
AU  - Milde T
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Pfister, Stefan M
AU  - Pfister SM
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Korshunov, Andrey
AU  - Korshunov A
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Kool, Marcel
AU  - Kool M
AD  - Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, 
      Germany; Cancer Consortium, Core Center Heidelberg, Heidelberg, Germany; 
      Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada; Alberta Children's Hospital Research Institute and Charbonneau 
      Cancer Institute, University of Calgary, Calgary, Alberta, Canada; Clinical 
      Cooperation Unit Pediatric Oncology, German Cancer Research Center, Heidelberg, 
      Germany; Department of Pediatric Oncology, Hematology and Immunology, Section of 
      Pediatric Brain Tumors, University Hospital Heidelberg, Heidelberg, Germany; 
      National Center for Tumor Diseases, Clinical Trial Center, Heidelberg, Germany; 
      Division of Neurosurgical Research, Department of Neurosurgery, University 
      Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit 
      Neuropathology, German Cancer Research Center, Heidelberg, Germany; Department of 
      Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (BI 6727)
RN  - 0 (Pteridines)
RN  - 0 (Topoisomerase I Inhibitors)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 7M7YKX2N15 (Topotecan)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Apoptosis/drug effects
MH  - Brain Neoplasms/*drug therapy/pathology
MH  - Cell Cycle/drug effects
MH  - Cell Proliferation/drug effects
MH  - Child, Preschool
MH  - Dactinomycin/*pharmacology
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplasms, Germ Cell and Embryonal/*drug therapy/pathology
MH  - Neuroectodermal Tumors, Primitive/*drug therapy/pathology
MH  - Pteridines/*pharmacology
MH  - Topoisomerase I Inhibitors/pharmacology
MH  - Topotecan/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
PMC - PMC5716199
OTO - NOTNLM
OT  - ETMR
OT  - actinomycin D
OT  - brain tumor
OT  - topotecan
OT  - volasertib
EDAT- 2017/05/10 06:00
MHDA- 2018/08/15 06:00
PMCR- 2018/11/01
CRDT- 2017/05/09 06:00
PHST- 2017/05/10 06:00 [pubmed]
PHST- 2018/08/15 06:00 [medline]
PHST- 2017/05/09 06:00 [entrez]
PHST- 2018/11/01 00:00 [pmc-release]
AID - 3803435 [pii]
AID - nox093 [pii]
AID - 10.1093/neuonc/nox093 [doi]
PST - ppublish
SO  - Neuro Oncol. 2017 Nov 29;19(12):1607-1617. doi: 10.1093/neuonc/nox093.