Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Considerations when treating high-grade pediatric glioma patients with immunotherapy.

ABSTRACT:

Introduction

Children with high-grade gliomas (pHGGs) represent a clinical population in substantial need of new therapeutic options given the inefficacy and toxicity of current standard-of-care modalities. Although immunotherapy has emerged as a promising modality, it has yet to elicit a significant survival benefit for pHGG patients. While preclinical studies address a variety of underlying challenges, translational clinical trial design and management also need to reflect the most updated progress and lessons from the field.

Areas covered

The authors will focus our discussion on the design of clinical trials, the management of potential toxicities, immune monitoring, and novel biomarkers. Clinical trial design should integrate appropriate patient populations, novel, and preclinically optimized trial design, and logical treatment combinations, particularly those which synergize with standard of care modalities. However, there are caveats due to the nature of immunotherapy trials, such as patient selection bias, evidenced by the frequent exclusion of patients on high-dose corticosteroids. Robust immune-modulating effects of modern immunotherapy can have toxicities. As such, it is important to understand and manage these, especially in pHGG patients.

Expert opinion

Adequate integration of these considerations should allow us to effectively gain insights on biological activity, safety, and biomarkers associated with benefits for patients.

SUBMITTER: Crotty E

PROVIDER: S-EPMC7880880 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Pediatric versus adult high grade glioma: Immunotherapeutic and genomic considerations.

Project description:High grade gliomas are identified as malignant central nervous tumors that spread rapidly and have a universally poor prognosis. Historically high grade gliomas in the pediatric population have been treated similarly to adult high grade gliomas. For the first time, the most recent classification of central nervous system tumors by World Health Organization has divided adult from pediatric type diffuse high grade gliomas, underscoring the biologic differences between these tumors in different age groups. The objective of our review is to compare high grade gliomas in the adult versus pediatric patient populations, highlighting similarities and differences in epidemiology, etiology, pathogenesis and therapeutic approaches. High grade gliomas in adults versus children have varying clinical presentations, molecular biology background, and response to chemotherapy, as well as unique molecular targets. However, increasing evidence show that they both respond to recently developed immunotherapies. This review summarizes the distinctions and commonalities between the two in disease pathogenesis and response to therapeutic interventions with a focus on immunotherapy.

| S-EPMC9722734 | biostudies-literature

PRMT5 promotes growth of pediatric high grade glioma.

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-11-22 | GSE261514 | GEO

Mutations in chromatin machinery and pediatric high-grade glioma.

Project description:Pediatric central nervous system tumors are the most common solid tumor of childhood. Of these, approximately one-third are gliomas that exhibit diverse biological behaviors in the unique context of the developing nervous system. Although low-grade gliomas predominate and have favorable outcomes, up to 20% of pediatric gliomas are high-grade. These tumors are a major contributor to cancer-related morbidity and mortality in infants, children, and adolescents, with long-term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. We review the current perspective on pediatric high-grade glioma genetics and epigenetics, and discuss the emerging and experimental therapeutics targeting the unique molecular abnormalities present in these deadly childhood brain tumors.

| S-EPMC4803494 | biostudies-literature

Immunotherapy and radiation for high-grade glioma: a narrative review

Project description:Glioblastoma and other high-grade gliomas (HGGs) are the most common and deadly primary brain tumors. Due to recent advances in immunotherapy and improved clinical outcomes in other disease sites, the study of immunotherapy in HGG has increased significantly. Herein, we summarize and evaluate existing evidence and ongoing clinical trials investigating the use of immunotherapy in the treatment of HGG, including therapeutic vaccination, immune checkpoint inhibition, adoptive lymphocyte transfer, and combinatorial approaches utilizing radiation and multiple modalities of immunotherapy. Special attention is given to the mechanisms by which radiation may improve immunogenicity in HGG, why this motivates the study of radiation in combination with immunotherapy, and how to determine optimal dosing and scheduling of radiation. Though larger randomized controlled trials have not consistently shown improvements in clinical outcomes, this area of research is still in its early stages and a number of important lessons can be taken away from the studies that have been completed to date. Many studies found a subset of patients who experienced durable responses, and analysis of their immune cells and tumor cells can be used to identify biomarkers that predict therapeutic response, as well as additional glioma-specific targets that can enhance therapeutic efficacy in a challenging tumor type.

| S-EPMC8797698 | biostudies-literature

Effect of disulfiram treatment on pediatric high grade glioma

Project description:RNA-seq analysis was performed to compare gene expression between glioma cells treated with disulfiram and untreated glioma cells.

2019-10-16 | GSE138863 | GEO

Single-cell ATAC-Seq of pediatric high-grade glioma

Project description:We performed scATAC-seq on glioblastoma tissue samples taken at time of initial surgical resection to map the global chromatin profiles of glioblastoma cells and associated non-neoplastic cells

2021-10-20 | GSE163655 | GEO

Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma.

Project description:Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.

| S-EPMC8452624 | biostudies-literature

Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments.

Project description:Pediatric high-grade gliomas (pHGG) are the leading cause of cancer-related death in children. These epigenetically dysregulated tumors often harbor mutations in genes encoding histone 3, which contributes to a stem cell-like, therapy-resistant phenotype. Furthermore, pHGG are characterized by a diffuse growth pattern, which, together with their delicate location, makes complete surgical resection often impossible. Radiation therapy (RT) is part of the standard therapy against pHGG and generally the only modality, apart from surgery, to provide symptom relief and a delay in tumor progression. However, as a single treatment modality, RT still offers no chance for a cure. As with most therapeutic approaches, irradiated cancer cells often acquire resistance mechanisms that permit survival or stimulate regrowth after treatment, thereby limiting the efficacy of RT. Various preclinical studies have investigated radiosensitizers in pHGG models, without leading to an improved clinical outcome for these patients. However, our recently improved molecular understanding of pHGG generates new opportunities to (re-)evaluate radiosensitizers in these malignancies. Furthermore, the use of radio-enhancing agents has several benefits in pHGG compared to other cancers, which will be discussed here. This review provides an overview and a critical evaluation of the radiosensitization strategies that have been studied to date in pHGG, thereby providing a framework for improving radiosensitivity of these rapidly fatal brain tumors.

| S-EPMC8047603 | biostudies-literature

Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma.

Project description:Pediatric high-grade glioma (HGG, WHO Grade III and IV) is a devastating brain tumor with a median survival of less than two years. PDGFRA is frequently mutated/ amplified in pediatric HGG, but the significance of this finding has not been fully characterized. We hypothesize that alterations of PDGFRA will promote distinct prognostic and treatment implications in pediatric HGG. In order to characterize the impact of PDGFR pathway alterations, we integrated genomic data from pediatric HGG patients (n=290) from multiple pediatric datasets and sequencing platforms. Integration of multiple human datasets showed that PDGFRA mutation, but not amplification, was associated with older age in pediatric HGG (P= <0.0001). In multivariate analysis, PDGFRA mutation was correlated with worse prognosis (P = 0.026), while PDGFRA amplification was not (P = 0.11). By Kaplan-Meier analysis, non-brainstem HGG with PDGFRA amplification carried a worse prognosis than non-brainstem HGG without PDGFRA amplification (P = 0.021). There were no pediatric patients with PDGFRA-amplified HGG that survived longer than two years. Additionally, we performed paired molecular profiling (germline / tumor / primary cell culture) and targeting of an infant thalamic HGG with amplification and outlier increased expression of PDGFRA. Dasatinib inhibited proliferation most effectively. In summary, integration of the largest genomic dataset of pediatric HGG to date, allowed us to highlight that PDGFRA mutation is found in older pediatric patients and that PDGFRA amplification is prognostic in non-brainstem HGG. Future precision-medicine based clinical trials for pediatric patients with PDGFRA-altered HGG should consider the optimized delivery of dasatinib.

| S-EPMC5323185 | biostudies-literature

Immunotherapy for High-Grade Gliomas: A Clinical Update and Practical Considerations for Neurosurgeons.

Project description:BackgroundThe current standard of care for patients with high-grade gliomas includes surgical resection, chemotherapy, and radiation; but even still most patients experience disease progression and succumb to their illness within a few years of diagnosis. Immunotherapy, which stimulates an anti-tumor immune response, has been revolutionary in the treatment of some hematologic and solid malignancies, generating substantial excitement for its potential for patients with glioblastoma. However, to date, the preclinical success of these approaches against high-grade glioma models has not been replicated in human clinical trials. Moreover, the complex response to these biologically active treatments can complicate management decisions, and the neurosurgical oncology community needs to be actively involved in and up to date on the use of these agents in patients with high-grade glioma. In this review, we discuss the challenges immunotherapy faces for high-grade gliomas, the completed and ongoing clinical trials for the major immunotherapies, and the nuances in management for patients being actively treated with one of these agents.MethodsWe reviewed the literature to summarize the current immunotherapy strategies for high-grade gliomas.ResultsPreclinical and clinical trials investigating dendritic cell and peptide vaccines, checkpoint inhibitors, and adoptive T cell therapy are highlighted in this review.ConclusionsAlthough immunotherapy has yet to fully fulfill its promise for patients with glioblastoma and improve patient outcomes, there is still excitement that these approaches will eventually lead to durable anti-tumor responses. As neurosurgeons, an understanding of the complex interactions between the standard of care therapies and the other medications used in the treatment arsenal for patients with high-grade brain tumors is crucial to the management of these patients.

| S-EPMC6642850 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data