Pediatric high-grade glioma: biologically and clinically in need of new thinking.
High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management.
Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
Chris
C
Jones
Division of Pediatric Hematology/Oncology, NYU Langone Medical Center, New York, NY, USA.
Matthias A
MA
Karajannis
Division of Pediatric Neurooncology, German Cancer Research Centre, Heidelberg, Germany.
David T W
DTW
Jones
Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Mark W
MW
Kieran
Department of Neurology & Neurological Sciences, Stanford University, Stanford, California, USA.
Michelle
M
Monje
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Suzanne J
SJ
Baker
Departments of Pediatrics and Pathology, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina, USA.
Oren J
OJ
Becher
Department of Neurology & Neurological Sciences, Stanford University, Stanford, California, USA.
Yoon-Jae
YJ
Cho
Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Nalin
N
Gupta
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada.
Cynthia
C
Hawkins
Neuro-oncology and Experimental Therapeutics, Great Ormond Street Hospital for Children, London, UK.
Darren
D
Hargrave
Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Daphne A
DA
Haas-Kogan
Department of Pediatrics, McGill University, Montreal, Canada.
Nada
N
Jabado
Brain Tumor Program, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Xiao-Nan
XN
Li
Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Sabine
S
Mueller
Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Theo
T
Nicolaides
Center for Neuroscience and Behavioral Medicine, Children's National Health System, Washington, District of Columbia, USA.
Roger J
RJ
Packer
Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Anders I
AI
Persson
Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Joanna J
JJ
Phillips
Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Erin F
EF
Simonds
Department of Biochemistry, NYU Langone Medical Center, New York, New York, USA.
James M
JM
Stafford
Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yujie
Y
Tang
Division of Pediatric Neurooncology, German Cancer Research Centre, Heidelberg, Germany.|Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
Stefan M
SM
Pfister
Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
William A
WA
Weiss
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002648:Child; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D060787:Neoplasm Grading; D011379:Prognosis
DIPG; clinical trials; genomics; glioma; pediatric