ArticleNeuro-oncology2017
Preclinical drug screen reveals topotecan, actinomycin D, and volasertib as potential new therapeutic candidates for ETMR brain tumor patients.
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Article in Neuro-oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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34citing papers in PubMed, 2 pooled it
2.2field-weighted citation impact, top 12% of its field
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Pooled it
- Extracranial extra-CNS spread of embryonal tumor with multilayered rosettes (ETMR): case series and systematic review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2018Pooled it
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.Nature cancer · 2025Article
- Review
- Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review).Molecular and clinical oncology · 2025Review
- Opportunities and challenges for patient-derived models of brain tumors in functional precision medicine.NPJ precision oncology · 2025Review
- Preclinical Assessment of Dactinomycin inCancers · 2025Article
- Multi-omics analysis revealed significant metabolic changes in brain cancer cells treated with paclitaxel and/or topotecan.Heliyon · 2024Article
- Review
- Integrated proteomics spotlight the proteasome as a therapeutic vulnerability in embryonal tumors with multilayered rosettes.Neuro-oncology · 2024Article
- PANCDR: precise medicine prediction using an adversarial network for cancer drug response.Briefings in bioinformatics · 2024Article
- Class I HDAC inhibitor entinostat synergizes with PLK1 inhibitors in MYC-amplified medulloblastoma cells.Journal of neuro-oncology · 2023Article
- Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.Cancers · 2023Review
- Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience.Children (Basel, Switzerland) · 2022Article
- Embryonal and non-meningothelial mesenchymal tumors of the central nervous system - Advances in diagnosis and prognostication.Brain pathology (Zurich, Switzerland) · 2022Review
- Promising Chemotherapy for Malignant Pediatric Brain Tumor in Recent Biological Insights.Molecules (Basel, Switzerland) · 2022Review
- PLK inhibitors come of age in pediatric brain tumors.Neuro-oncology · 2022Article
- Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial.Neuro-oncology · 2022Article
- Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Christin SchmidtDivision 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.
Nil A SchubertDivision 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.
Sebastian BrabetzDivision 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.
Norman MackDivision 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.
Benjamin SchwalmDivision 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.
Jennifer A ChanDivision 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.
Florian SeltDivision 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.
Christel Herold-MendeDivision 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.
Olaf WittDivision 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.
Till MildeDivision 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.
Stefan M PfisterDivision 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.
Andrey KorshunovDivision 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.
Marcel KoolDivision 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.
National Center for Tumor Diseases · DEUniversity of Calgary · CAHeidelberg University · DEUniversity Hospital Heidelberg · DEAlberta Children's Hospital · CA
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEmbryonal 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.
methodsWe 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.
resultsBT183 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.
conclusionsWe have identified several promising candidates for combination therapies in future clinical trials for ETMR patients.
Indexed as
AnimalsAntibiotics, AntineoplasticApoptosisBrain NeoplasmsCell CycleCell ProliferationChild, PreschoolDactinomycinFemaleHumansMiceMice, Inbred NODMice, SCIDNeoplasms, Germ Cell and EmbryonalNeuroectodermal Tumors, PrimitivePteridinesAntibiotics, AntineoplasticBI 6727DactinomycinPteridinesTopoisomerase I InhibitorsTopotecanactinomycin Dbrain tumorETMRtopotecanvolasertib
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