title: Molecular mechanisms and therapeutic targets in pediatric brain tumors.
abstract: Brain tumors are among the leading causes of cancer-related deaths in children. Although surgery, aggressive radiation, and chemotherapy have improved outcomes, many patients still die of their disease. Moreover, those who survive often suffer devastating long-term side effects from the therapies. A greater understanding of the molecular underpinnings of these diseases will drive the development of new therapeutic approaches. Advances in genomics and epigenomics have provided unprecedented insight into the molecular diversity of these diseases and, in several cases, have revealed key genes and signaling pathways that drive tumor growth. These not only serve as potential therapeutic targets but also have facilitated the creation of animal models that faithfully recapitulate the human disease for preclinical studies. In this Review, we discuss recent progress in understanding the molecular basis of the three most common malignant pediatric brain tumors-medulloblastoma, ependymoma, and high-grade glioma-and the implications for development of safer and more effective therapies.
authors.affiliation: Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Kun-Wei
authors.identifier: http://orcid.org/0000-0003-4944-1758
authors.initials: KW
authors.lastname: Liu
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Centre (Deutsches Krebsforschungszentrum, DKFZ) and Heidelberg University Hospital, D-69120 Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, University Hospital, D-69120 Heidelberg, Germany.|German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung, DKTK), Core Center Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Kristian W
authors.identifier: http://orcid.org/0000-0002-3562-6121
authors.initials: KW
authors.lastname: Pajtler
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Centre (Deutsches Krebsforschungszentrum, DKFZ) and Heidelberg University Hospital, D-69120 Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, University Hospital, D-69120 Heidelberg, Germany.|German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung, DKTK), Core Center Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Worst
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Centre (Deutsches Krebsforschungszentrum, DKFZ) and Heidelberg University Hospital, D-69120 Heidelberg, Germany. rwreya@sbpdiscovery.org s.pfister@dkfz-heidelberg.de.|Department of Pediatric Oncology, Hematology and Immunology, University Hospital, D-69120 Heidelberg, Germany.|German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung, DKTK), Core Center Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Stefan M
authors.identifier: http://orcid.org/0000-0002-5447-5322
authors.initials: SM
authors.lastname: Pfister
authors.affiliation: Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. rwreya@sbpdiscovery.org s.pfister@dkfz-heidelberg.de.
authors.forename: Robert J
authors.identifier: http://orcid.org/0000-0002-7463-8352
authors.initials: RJ
authors.lastname: Wechsler-Reya
mesh_terms: D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D004806:Ependymoma / Q000188:drug therapy / Q000235:genetics*; D005910:Glioma / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy / Q000235:genetics*; D058990:Molecular Targeted Therapy / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor