Combination drug therapy for childhood brain tumors shows promise in laboratory models

(Johns Hopkins Medicine) In experiments with human cells and mice, researchers at the Johns Hopkins Kimmel Cancer Center report evidence that combining the experimental cancer medication TAK228 (also called sapanisertib) with an existing anti-cancer drug called trametinib may be more effective than either drug alone in decreasing the growth of pediatric low-grade gliomas.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news

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(NIH/National Institute of Neurological Disorders and Stroke) Every year, 150 to 300 children in the United States are diagnosed with diffuse intrinsic pontine gliomas (DIPGs), aggressive and lethal tumors that grow deep inside the brain, for which there are no cures. In a study funded by the National Institutes of Health, researchers showed that experimental drugs designed to lower the body's natural production of alpha-ketoglutarate extended the lives of mice harboring DIPG tumors by slowing the growth of the cancer cells.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Contributors : Anhaid Ehteda ; Sandy Simon ; Laura Franshaw ; Federico M Giorgi ; Jie Liu ; Elisha Hayden ; Swapna Joshi ; Chi N Pang ; Ruby Pandher ; Chelsea Mayoh ; Aaminah Khan ; Caitlin Ung ; Ornella Tolhurst ; Anne Kankean ; Anjana Gopalakrishnan ; Peter Trebilcock ; Katerina Gurova ; Andrei Gudkov ; Murray D Norris ; Michelle Haber ; Orazio Vittorio ; Maria Tsoli ; David S ZieglerSeries Type : Expression profiling by arrayOrganism : Homo sapiensDiffuse intrinsic pontine glioma (DIPG) is an aggressive and incurable childhood brain tumor for which new treatments are needed. A high throughput drug screen of 3600 pharmac...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
As a highly aggressive pediatric brainstem tumor, diffuse intrinsic pontine glioma (DIPG) accounts for 10% to 20% of childhood brain tumors. The survival rate for DIPG remains very low, with a median survival time as less than one year even under radiotherapy, the current standard treatment. Moreover, over than 250 clinical trials have failed when trying to improve the survival compared to radiotherapy. The sphingolipid metabolism and related signaling pathways have been found closely related to cancer cell survival; however, the sphingolipid metabolism targeted therapies have never been investigated in DIPG. In the curren...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper 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
CONCLUSIONS: On brain MR imaging, these patients have both highly characteristic intra-axial tumors (typically multifocal high-grade gliomas) and nonspecific findings, some of which might represent early stages of neoplastic transformation. The incidence of developmental venous anomalies is high in these patients for unclear reasons. Awareness of these imaging findings, especially in combination, is important to raise the suspicion of constitutional mismatch repair deficiency in routine diagnostic imaging evaluation or surveillance imaging studies of asymptomatic carriers because early identification of the phenotypic &quo...
Source: American Journal of Neuroradiology - Category: Radiology Authors: Tags: PEDIATRICS Source Type: research
Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor which accounts for about 10-20% of childhood brain tumors. The survival rate for DIPG remains very poor, with a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of a large number of clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care for DIPG. In the current study, we screened a natural product library and for the first time identified 6 natural compounds displaying inhibitory effects on DIPG pr...
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research
BACKGROUND AND PURPOSE: Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma. MATERIALS AND METHODS: A clinical trial using the poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor veliparib concurrently with radiation therapy, followed by maintenance therapy with veliparib + temozolomide, in child...
Source: American Journal of Neuroradiology - Category: Radiology Authors: Tags: FUNCTIONAL Source Type: research
(Institute of Cancer Research) Brain cancer in infants is biologically distinct from other childhood brain tumors and could be successfully treated with targeted drugs, a new study has shown. In the largest and most comprehensive study of infant gliomas to date, scientists found that these tumors are molecularly different from those in older children, helping explain why they tend to be less aggressive.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic–pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Abstract PURPOSE: Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor. Patients with BRAF V600 mutation-positive pLGG may benefit from treatment with dabrafenib. Part 2 of a phase I/IIa study, open-label study (NCT01677741) explores the activity and safety of dabrafenib treatment in these patients. PATIENTS AND METHODS: Patients ages 1 to
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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