Oncogene· 2026Q1
Beyond the blood-brain barrier: humanised mice, the missing link in glioblastoma research
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- Q1SCImago
- 2026year
Short summary
Humanised mouse models accurately replicate human glioblastoma (GBM) by preserving crucial blood-brain barriers and recapitulating immune-tumor microenvironment interactions, offering a more translatable preclinical platform than conventional animal or ex vivo models.
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Key points
- Conventional GBM models lack the complexity of the tumor microenvironment and central nervous system treatment barriers.
- Humanised mouse models replicate human GBM's molecular, pathological, and immunological features.
- These models preserve blood-brain barriers, crucial for studying drug delivery to the brain.
- Humanised mice allow for the study of in vivo immune system and tumor microenvironment interactions.
- They closely reproduce human immune cell infiltration, aiding research into therapeutic resistance.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Glioblastoma (GBM) remains a major challenge in neuro-oncology, associated with a high rate of mortality despite decades of intensive research and therapeutic advancements, underscoring the urgent need for innovative preclinical platforms that can more accurately recapitulate the biological and pathological features of human disease. While conventional animal models have contributed to our understanding of GBM biology and the evaluation of treatment efficacy, they fail to capture the full complexity and heterogeneity of the tumour microenvironment (TME). Ex vivo models are associated with certain advantages in this context; however, they can not mirror the complex dynamic and multicellular interactions present in living organisms, particularly the critical treatment barriers unique to the central nervous system: the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB) and blood-meningeal barrier (BMB). In response to these limitations, humanised mouse models have emerged as an advanced platform capable of faithfully mimicking the molecular, pathological and immunological features of human GBM. These models enable the replication of complex in vivo crosstalk between the immune system and the TME, while preserving the relevant treatment barriers that govern drug delivery to the brain. Accumulating evidence indicates that humanised mouse models closely reproduce the infiltration of human immune components into the TME, enabling the study of clinically relevant interactions that contribute to therapeutic resistance and treatment failure in GBM. This review aims to provide a comprehensive and systematic overview of the currently employed humanised mouse models in GBM research, highlighting their applications and comparative advantages. Finally, we evaluate the opportunities and challenges associated with each model and discuss future directions to increase the translational relevance and predictive power of preclinical GBM research.
The authors' abstract, as published at the source. Oncogene, 2026 · DOI ↗
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