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Updated: Aug 12, 2026
Establishing Intracranial Brain Tumor Xenografts With Subsequent Analysis of Tumor Growth and Response to Therapy using Bioluminescence Imaging
Published on: July 14, 2010
Therapeutic analysis of in vitro and in vivo brain tumor models
J M Schuster1, H S Friedman, D D Bigner
1Department of Pathology, Duke University Medical Center, Durham, North Carolina.
Abstract:
Virtually all brain tumor models studied to date have demonstrated the activity of the nitrosoureas, an observation confirmed in a cohort of adult patients with high-grade gliomas. However, studies with animal brain tumor models have not led to the selection of other clinically active agents (with the possible exception of AZQ), leading investigators to conduct experiments with human CNS tumor-derived cell lines and xenografts. These studies have identified agents subsequently shown to be active in phase II clinical trials against high-grade glioma and medulloblastoma. Clinical phase III trials in progress will demonstrate if these agents result in increased disease-free survival, which is the ultimate goal of all preclinical therapeutic studies. Future research with these laboratory models may ultimately allow the definition of the mechanisms of drug resistance and the identification of modulations effective in bypassing or reversing this resistance.
Insights
Brain tumor models show nitrosourea activity in patients with high-grade gliomas. Further research using human cell lines and xenografts identified new agents for clinical trials, aiming to improve disease-free survival.
Area of Science:
- Neuro-oncology
- Cancer Therapeutics
- Preclinical Research
Background:
- Nitrosoureas demonstrate consistent activity across various brain tumor models and in adult patients with high-grade gliomas.
- Limitations in animal models for identifying novel therapeutic agents prompted research using human central nervous system (CNS) tumor-derived cell lines and xenografts.
Purpose of the Study:
- To identify novel therapeutic agents for brain tumors beyond nitrosoureas.
- To validate findings from human CNS tumor models in clinical trials.
- To explore mechanisms of drug resistance in brain tumors.
Main Methods:
- Utilizing human CNS tumor-derived cell lines and xenografts for drug screening.
- Conducting preclinical therapeutic studies.
- Initiating clinical phase II and phase III trials for promising agents.
Main Results:
- Human CNS tumor models identified agents with demonstrated activity in phase II clinical trials for high-grade glioma and medulloblastoma.
- Ongoing clinical phase III trials are evaluating the efficacy of these agents in improving disease-free survival.
Conclusions:
- Human CNS tumor models are valuable for identifying clinically active agents against brain tumors.
- Future research should focus on understanding and overcoming drug resistance mechanisms to improve patient outcomes.
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