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Updated: May 23, 2026
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Patient-derived tumour xenografts as models for oncology drug development
John J Tentler1, Aik Choon Tan, Colin D Weekes
1Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO 80045, USA.
Abstract:
Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. In an effort to address these shortcomings, there has been a recent increase in the use of patient-derived tumour xenografts (PDTX) engrafted into immune-compromised rodents such as athymic nude or NOD/SCID mice for preclinical modelling. Numerous tumour-specific PDTX models have been established and, importantly, they are biologically stable when passaged in mice in terms of global gene-expression patterns, mutational status, metastatic potential, drug responsiveness and tumour architecture. These characteristics might provide significant improvements over standard cell-line xenograft models. This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.
Insights
Patient-derived tumor xenografts (PDTX) offer improved preclinical cancer models. These models maintain biological stability, enhancing their potential for predicting clinical drug activity in cancer patients.
Area of Science:
- Oncology
- Translational Research
- Preclinical Drug Development
Background:
- Oncology drug development faces challenges due to unreliable preclinical models.
- Patient-derived tumor xenografts (PDTX) are increasingly used to bridge this gap.
- PDTX models are engrafted into immune-compromised rodents for preclinical evaluation.
Purpose of the Study:
- To review the opportunities and limitations of PDTX models in cancer drug development.
- To illustrate PDTX model utility with specific disease examples.
- To discuss predictive biomarker development and future applications for PDTX models.
Main Methods:
- Establishment of numerous tumor-specific PDTX models.
- Biological characterization of PDTX models, including gene expression, mutational status, and drug responsiveness.
- Comparison of PDTX models with standard cell-line xenograft models.
Main Results:
- PDTX models demonstrate biological stability across passages.
- Key characteristics like gene expression, mutational status, and drug response are maintained.
- PDTX models show potential for improved prediction of clinical drug activity.
Conclusions:
- PDTX models represent a significant advancement over traditional xenograft models.
- These models offer enhanced reliability for preclinical cancer drug testing.
- Further development and application of PDTX models are crucial for advancing oncology therapeutics.
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