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Updated: Dec 2, 2025
Establishment of Orthotopic Patient-derived Xenograft Models for Brain Tumors using a Stereotaxic Device
Published on: May 2, 2025
Pre-clinical tumor models of primary brain tumors: Challenges and opportunities
Farhana Akter1, Brennan Simon1, Nadine Leonie de Boer2
1Center for Stem Cell Therapeutics and Imaging (CSTI), Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States of America; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States of America.
Abstract:
Primary brain tumors are a heterogeneous group of malignancies that originate in cells of the central nervous system. A variety of models tractable for preclinical studies have been developed to recapitulate human brain tumors, allowing us to understand the underlying pathobiology and explore potential treatments. However, many promising therapeutic strategies identified using preclinical models have shown limited efficacy or failed at the clinical trial stage. The inability to develop therapeutic strategies that significantly improve survival rates in patients highlight the compelling need to revisit the design of currently available animal models and explore the use of new models that allow us to bridge the gap between promising preclinical findings and clinical translation. In this review, we discuss current strategies used to model glioblastoma, the most malignant brain tumor in adults and highlight the shortcomings of specific models that must be circumvented for the development of innovative therapeutic strategies.
Insights
Developing effective brain tumor treatments requires better animal models. Current models often fail in clinical trials, necessitating new approaches for improved glioblastoma therapy translation.
Area of Science:
- Neuro-oncology
- Translational research
- Cancer modeling
Background:
- Primary brain tumors are diverse central nervous system malignancies.
- Preclinical models aid in understanding brain tumor pathobiology and testing treatments.
- Many treatments successful in preclinical models fail in human clinical trials.
Purpose of the Study:
- To review current strategies for modeling glioblastoma, the most aggressive adult brain tumor.
- To identify shortcomings in existing animal models for brain tumor research.
- To emphasize the need for improved models to bridge the gap between preclinical findings and clinical translation.
Main Methods:
- Literature review of preclinical brain tumor models.
- Analysis of glioblastoma modeling techniques.
- Discussion of translational challenges in neuro-oncology.
Main Results:
- Existing preclinical models have limitations that hinder therapeutic development.
- Current models do not fully recapitulate human glioblastoma complexity.
- A gap exists between promising preclinical results and clinical efficacy.
Conclusions:
- Improved animal models are crucial for advancing glioblastoma treatment strategies.
- Revisiting and innovating brain tumor model design is essential for clinical translation.
- Overcoming model limitations will facilitate the development of more effective therapies.
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