Study sheds light on treatment options for devastating childhood brain cancer

(Washington University School of Medicine) Research from Washington University School of Medicine in St. Louis suggests that children with average risk medulloblastoma can receive radiation to a smaller volume of the brain at the end of a six-week course of treatment and still maintain the same disease control as those receiving radiation to a larger area. But the dose of preventive radiation treatments given to the whole brain and spine over the six-week regimen cannot be reduced without reducing survival.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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The sonic hedgehog subtype of medulloblastoma (SHH MB) is associated with treatment failure and poor outcome. Current strategies utilizing whole brain radiation therapy result in deleterious off-target effects on the normal developing childhood brain. Most conventional chemotherapies remain limited by ineffective blood–brain barrier (BBB) penetrance. These challenges signify an unmet...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Biological Sciences Source Type: research
The impact of the total number of administrations and the cumulative dosage of anesthetics and sedatives on the developing brain is not a new topic for readers of The Journal (J Pediatr 2019;204:285 –90). In this volume, Jacola et al report the effects of anesthesia exposure in 111 children with medulloblastoma from a retrospective, secondary analysis of patients at St. Jude Children's Research Hospital enrolled on a multisite clinical trial (https://clinicaltrials.gov/ct2/show/NCT00085202). The children were all treated with surgical resection of tumor, followed by radiotherapy and chemotherapy.
Source: The Journal of Pediatrics - Category: Pediatrics Authors: Tags: The Editors' Perspectives Source Type: research
Abstract Eliminating cancer was once thought of as a war. This analogy is still apt today; however, we now realize that cancer is a much more formidable enemy than scientists originally perceived, and in some cases, it harbors a profound ability to thwart our best efforts to defeat it. However, before we were aware of the complexity of cancer, chemotherapy against childhood acute lymphoblastic leukemia (ALL) was successful because it applied the principles of pharmacology. Herein, we provide a historic perspective of the experience at St. Jude Children's Research Hospital. In 1962, when the hospital opened, fewer ...
Source: Pharmacological Reviews - Category: Drugs & Pharmacology Authors: Tags: Pharmacol Rev Source Type: research
Abstract Pediatric brain tumors are the leading cause of cancer-related death in children. Patient-derived orthotopic xenografts (PDOX) of childhood brain tumors have recently emerged as a biologically faithful vehicle for testing novel and more effective therapies. Herein, we provide the histopathological and molecular analysis of 37 novel PDOX models generated from pediatric brain tumor patients treated at St. Jude Children ’s Research Hospital. Using a combination of histopathology, whole-genome and whole-exome sequencing, RNA-sequencing, and DNA methylation arrays, we demonstrate the overall fidelity and inter-...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
ConclusionsWe propose that pathogenicPTEN variants may predispose to medulloblastoma, and show that remission was reached with current treatment protocols. ThePTEN gene should be included in the genetic testing provided to patients who develop medulloblastoma at an early age. We recommend brain magnetic resonance imaging upon an unexpected acceleration of growth of head circumference for pediatric patients harboring pathogenic germlinePTEN variants.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
In this study, we characterized the role of ERBB4 during cerebellum development and medulloblastoma progression paying particular interests to its role in CGNPs and medulloblastoma stem cells (MBSCs). Our results show that ERBB4 is expressed in the CGNPs during cerebellum development where it plays a critical role in migration, apoptosis and differentiation. Similarly, it is enriched in the population of MBSCs, where also controls those critical processes, as well as self-renewal and tumor initiation for medulloblastoma progression. These results are translated to clinical samples where high levels of ERBB4 correlate with ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we characterized the role of ERBB4 during cerebellum development and medulloblastoma progression paying particular interests to its role in CGNPs and medulloblastoma stem cells (MBSCs). Our results show that ERBB4 is expressed in the CGNPs during cerebellum development where it plays a critical role in migration, apoptosis and differentiation. Similarly, it is enriched in the population of MBSCs, where also controls those critical processes, as well as self-renewal and tumor initiation for medulloblastoma progression. These results are translated to clinical samples where high levels of ERBB4 correlate with ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Medulloblastoma (MB) is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. DNA methylation profiling has rapidly advanced our understanding of MB pathogenesis at the molecular level, but assessments in Saudi Arabian (SA)-MB cases are sparse. MBs can be sub-grouped according to methylation patterns from FPPE samples into Wingless (WNT-MB), Sonic Hedgehog (SHH-MB), Group 3 (G3), and Group 4 (G4) tumors. The WNT-MB and SHH-MB subgroups are characterized by gain-of function mutations that activate oncogenic cell signaling, whilst G3/G4 tumors show recurrent chromosomal a...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Baoli Hu Medulloblastoma, the most common pediatric malignant brain tumor, continues to have a high rate of morbidity and mortality in childhood. Recent advances in cancer genomics, single-cell sequencing, and sophisticated tumor models have revolutionized the characterization and stratification of medulloblastoma. In this review, we discuss heterogeneity associated with four major subgroups of medulloblastoma (WNT, SHH, Group 3, and Group 4) on the molecular and cellular levels, including histological features, genetic and epigenetic alterations, proteomic landscape, cell-of-origin, tumor microenvironment, and therap...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractPediatric brain tumors are the leading cause of childhood cancer mortality with medulloblastoma (MB) representing the most frequent malignant tumor. Although standardization of therapy resulted in a 2-fold reduction in mortality in patients with MB by 2002, it became clear that further improvements in clinical outcome would require a deeper understanding of the biology of MB. Employing the four main molecular MB subgroups (Wnt, Shh, Group 3 and Group 4), a restratification into clinicogenomic risk categories quantified an unacceptable survival for the high-risk group, urging researchers to focus their efforts towar...
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research
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