Document Type
Article
Publication Date
7-2-2025
Identifier
DOI: 10.3390/cancers17132221; PMCID: PMC12248539
Abstract
Pediatric high-grade gliomas (pHGGs), particularly diffuse midline gliomas (DMGs), are among the most lethal brain tumors due to poor survival and resistance to therapies. DMGs possess a distinct genetic profile, primarily driven by hallmark mutations such as H3K27M, ACVR1, and PDGFRA mutations/amplifications and TP53 inactivation, all of which contribute to tumor biology and therapeutic resistance. Developing physiologically relevant preclinical models that replicate both tumor biology and the tumor microenvironment (TME) is critical for advancing effective treatments. This review highlights recent progress in in vitro, ex vivo, and in vivo models, including patient-derived brain organoids, genetically engineered mouse models (GEMMs), and region-specific midline organoids incorporating SHH, BMP, and FGF2/8/19 signaling to model pontine gliomas. Key genetic alterations can now be introduced using lipofectamine-mediated transfection, PiggyBac plasmid systems, and CRISPR-Cas9, allowing the precise study of tumor initiation, progression, and therapy resistance. These models enable the investigation of TME interactions, including immune responses, neuronal infiltration, and therapeutic vulnerabilities. Future advancements involve developing immune-competent organoids, integrating vascularized networks, and applying multi-omics platforms like single-cell RNA sequencing and spatial transcriptomics to dissect tumor heterogeneity and lineage-specific vulnerabilities. These innovative approaches aim to enhance drug screening, identify new therapeutic targets, and accelerate personalized treatments for pediatric gliomas.
Journal Title
Cancers (Basel)
Volume
17
Issue
13
PubMed ID
40647519
Keywords
GEMMs; diffuse midline gliomas; immunocompetent mouse model of DMGs; in utero electroporation; pHGGs
Recommended Citation
Faisal SM, Yadav M, Gibson GR, et al. Current Landscape of Preclinical Models for Pediatric Gliomas: Clinical Implications and Future Directions. Cancers (Basel). 2025;17(13):2221. Published 2025 Jul 2. doi:10.3390/cancers17132221
Comments
Grants and funding
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Publisher's Link: https://www.mdpi.com/2072-6694/17/13/2221