ArticleCancer research2016
A Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found In Vivo.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 417 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
417 citing papers in PubMed, 2 syntheses or guidelines pooled it, 628 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine.Cellular oncology (Dordrecht, Netherlands) · 2025Pooled it
- Improved Method for Obtaining Patient-Derived Glioblastoma Organoid and Primary Cells: A Generic and Simplified Approach for Intracranial Tumor With Minimized Input.CNS neuroscience & therapeutics · 2026Article
- A patient-derived organoid platform for predominantly posterior fossa adult ependymoma: histopathologic preservation, culture-associated transcriptomic remodeling, and in vivo tumorigenicity.Journal of neuro-oncology · 2026Article
- Patient-derived tissue cultures complement neurospheres for preclinical evaluation of AAV-mediated gene delivery in glioblastoma.Journal of neuro-oncology · 2026Article
- Flash Assembloids: A Rapid Biofabrication of a Platform for Modeling Early Glioblastoma Invasion at the Glioblastoma-Brain Organoid Interfaces.Advanced healthcare materials · 2026Article
- Constructing anTranslational cancer research · 2026Article
- Construction Strategies, Microenvironmental Modelling and Precision-Therapy Applications of Glioma Organoid Models.Cancers · 2026Review
- Targeting mitotic kinesin KIF20A: A differentiation-based therapeutic strategy for glioblastoma stem/progenitor cells.Stem cell reports · 2026Article
- Modeling gliomas with organoids: Classification, fidelity, and guidelines for translational neuro-oncology.Neuro-oncology · 2026Review
- From patient to tumor organoid: Culture protocol choice controls glioblastoma tumor architecture and identity.Brain pathology (Zurich, Switzerland) · 2026Article
- Patient-derived organoids predict personalized drug response and reveal alternative therapeutic options in glioblastoma.Cell reports. Medicine · 2026Article
- Brain organoids and genome editing: A new era in understanding human brain development and disorders.Neural regeneration research · 2026Article
- EGFR-dependent delivery of phosphorylated IGFBP3 by cancer stem cells drives chemotherapy resistance in colorectal cancer.Cell death & disease · 2026Article
- Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- NeuroD1 gene therapy inhibits glioma growth and extends life span throughMolecular therapy. Oncology · 2026Article
- AAV immuno-gene therapy platform delivering vectorized cytokines defines a new modality for high-grade glioma treatment.Molecular therapy. Oncology · 2026Article
- Organoids to Model Tumor Microenvironment in Progression of Pathogenesis and Treatment Resistance in Glioblastoma Multiforme.Brain sciences · 2026Review
- Organoids in cancer therapy: translational applications and clinical promise.Molecular cancer · 2026Review
- Modelling brain tumours with organoids: towards precision medicine in neuro-oncology.Nature reviews. Neurology · 2026Review
357 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Many cancers feature cellular hierarchies that are driven by tumor-initiating cancer stem cells (CSC) and rely on complex interactions with the tumor microenvironment. Standard cell culture conditions fail to recapitulate the original tumor architecture or microenvironmental gradients and are not designed to retain the cellular heterogeneity of parental tumors. Here, we describe a three-dimensional culture system that supports the long-term growth and expansion of tumor organoids derived directly from glioblastoma specimens, including patient-derived primary cultures, xenografts, genetically engineered glioma models, or patient samples. Organoids derived from multiple regions of patient tumors retain selective tumorigenic potential. Furthermore, organoids could be established directly from brain metastases not typically amenable to in vitro culture. Once formed, tumor organoids grew for months and displayed regional heterogeneity with a rapidly dividing outer region of SOX2(+), OLIG2(+), and TLX(+) cells surrounding a hypoxic core of primarily non-stem senescent cells and diffuse, quiescent CSCs. Notably, non-stem cells within organoids were sensitive to radiotherapy, whereas adjacent CSCs were radioresistant. Orthotopic transplantation of patient-derived organoids resulted in tumors displaying histologic features, including single-cell invasiveness, that were more representative of the parental tumor compared with those formed from patient-derived sphere cultures. In conclusion, we present a new ex vivo model in which phenotypically diverse stem and non-stem glioblastoma cell populations can be simultaneously cultured to explore new facets of microenvironmental influences and CSC biology. Cancer Res; 76(8); 2465-77. ©2016 AACR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.