3D Models as Personalized Models for Paediatric Brain Cancer

Paediatric brain tumours remain among the most challenging cancers to treat, due to developmental context, heterogeneity, and the limited predictive power of conventional two-dimensional (2D) culture and some preclinical models. Three-dimensional (3D) systems, including patient-derived tumour organoids/explants, stem cell-derived neural organoids and assembloids, and engineered microenvironments, offer more tissue-relevant platforms to study tumour biology and therapy response. This Research Topic will focus on developing and applying these approaches as patient-relevant (“personalized”) models for mechanistic discovery, therapy response profiling, and biomarker development in paediatric brain tumours.We welcome submissions spanning model establishment and optimization; organoid/assembloid engineering to capture neural lineage context; and quantitative imaging, functional perturbation (e.g., CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats-based genome editing), and multi-omics (i.e., combined large-scale “omics” profiling such as genomics/transcriptomics/proteomics; including single-cell and spatial approaches) that connect phenotype to mechanism. We particularly encourage studies on epigenetic and transcriptional regulation of tumour cell states and plasticity, and how these programs change under therapy or microenvironmental pressures.Work incorporating brain tumour–relevant niche features is strongly encouraged, including microglia/brain-resident immune components, neuron–tumour interactions and activity-dependent effects, blood–brain barrier (BBB) and perfusable vascular features, hypoxia/nutrient gradients, and extracellular matrix (ECM)/biomaterials tuned to brain-like properties. In addition to organoids, we welcome complementary 3D platforms such as patient-derived slice cultures, tumour-on-chip/microfluidic systems, hydrogel-based 3D culture, and multi-compartment co-culture assembloids (e.g., tumour–neural–vascular–immune).Therapy-focused studies are encouraged, including 3D modelling of response and resistance to radiotherapy/proton and radiosensitizers, targeted therapies and rational combinations, and—where model-appropriate—immunotherapies (e.g., CAR-T: Chimeric Antigen Receptor T-cell/bispecific approaches, oncolytic viruses), as well as delivery-relevant questions linked to BBB constraints.To support wider adoption, this Topic also encourages work on standardization, benchmarking, scalability, and quality control (QC), including defined/xeno-free (free of animal-derived components) workflows and bioprocessing approaches where relevant. Overall, the collection aims to advance robust 3D platforms that better reflect paediatric brain tumour biology and improve the predictive value of preclinical testing.Topics of interest include (but are not limited to)Patient-derived paediatric brain tumour organoids/explants and slice culturesStem cell-derived neural/hindbrain/cerebellar organoids and assembloids (tumour + neural + vascular/immune compartments)Tumour-on-chip/microfluidic and perfusion-enabled 3D platforms; BBB-informed modelsHydrogel/biomaterial systems reflecting brain ECM mechanics/compositionMicroglia and brain-immune interactions; neuron–tumour crosstalk and activity-dependent biologyVascular/endothelial biology, angiogenesis, hypoxia gradients, and vascular targeting strategiesTherapy testing and resistance: radiotherapy/proton, targeted therapy combinations, and model-appropriate immunotherapy/oncolytic approachesSingle-cell/spatial multi-omics, live/four-dimensional (4D) imaging (3D over time; the 4th dimension is time), CRISPR perturbations, and quantitative phenotypingReproducibility and scalability: Standard Operating Procedures (SOPs), benchmarking/QC metrics, automation-ready formats, defined media Topic editors: Teresa P. Silva, Joseph Wragg, Grace Cooksley Source: https://www.frontiersin.org/research-topics/78052/3d-models-as-personalized-models-for-paediatric-brain-cancer