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Updated: Nov 19, 2025
The Establishment and Utilization of Patient Derived Xenograft Models of Central Nervous System Metastasis
Published on: May 7, 2021
Development and characterization of patient-derived xenografts from non-small cell lung cancer brain metastases
Andrew M Baschnagel1,2, Saakshi Kaushik3, Arda Durmaz4
1Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, K4/B100-0600, Madison, WI, 53792, USA. baschnagel@humonc.wisc.edu.
Abstract:
Non-small cell lung cancer (NSCLC) brain metastasis cell lines and in vivo models are not widely accessible. Herein we report on a direct-from patient-derived xenograft (PDX) model system of NSCLC brain metastases with genomic annotation useful for translational and mechanistic studies. Both heterotopic and orthotopic intracranial xenografts were established and RNA and DNA sequencing was performed on patient and matching tumors. Morphologically, strong retention of cytoarchitectural features was observed between original patient tumors and PDXs. Transcriptome and mutation analysis revealed high correlation between matched patient and PDX samples with more than more than 95% of variants detected being retained in the matched PDXs. PDXs demonstrated response to radiation, response to selumetinib in tumors harboring KRAS G12C mutations and response to savolitinib in a tumor with MET exon 14 skipping mutation. Savolitinib also demonstrated in vivo radiation enhancement in our MET exon 14 mutated PDX. Early passage cell strains showed high consistency between patient and PDX tumors. Together, these data describe a robust human xenograft model system for investigating NSCLC brain metastases. These PDXs and cell lines show strong phenotypic and molecular correlation with the original patient tumors and provide a valuable resource for testing preclinical therapeutics.
Insights
Researchers developed a new patient-derived xenograft (PDX) model for non-small cell lung cancer (NSCLC) brain metastases. This model accurately reflects patient tumors and is valuable for preclinical drug testing in brain metastasis research.
Area of Science:
- Oncology
- Translational Research
- Genomics
Background:
- Non-small cell lung cancer (NSCLC) brain metastases lack accessible cell lines and in vivo models.
- Developing reliable models is crucial for advancing translational and mechanistic studies.
Purpose of the Study:
- To establish and characterize a direct patient-derived xenograft (PDX) model system for NSCLC brain metastases.
- To provide a resource for preclinical therapeutic testing and mechanistic investigations.
Main Methods:
- Establishment of heterotopic and orthotopic intracranial xenografts from patient-derived NSCLC brain metastases.
- Comprehensive genomic analysis (RNA and DNA sequencing) of matched patient tumors and PDXs.
- Evaluation of PDX response to radiation and targeted therapies (selumetinib, savolitinib).
Main Results:
- PDX models exhibited strong morphological retention of original patient tumor features.
- High molecular correlation (>95% variant retention) between patient tumors and matched PDXs was observed.
- PDXs responded to radiation, selumetinib (KRAS G12C), and savolitinib (MET exon 14 skipping), with savolitinib showing in vivo radiation enhancement.
Conclusions:
- A robust PDX model system for NSCLC brain metastases has been developed, showing high phenotypic and molecular fidelity to patient tumors.
- These PDX models and derived cell lines serve as a valuable preclinical resource for investigating NSCLC brain metastases and testing novel therapeutics.
- The model system facilitates translational research and mechanistic studies for targeted therapies in NSCLC brain metastasis.
