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  • Review Article
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Patient-derived tumour xenografts as models for oncology drug development

Nature Reviews Clinical Oncology volume 9, pages 338–350 (2012)Cite this article

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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.

Key Points

  • Many preclinical animal models fail to accurately predict the clinical efficacy of novel anticancer agents, largely due to their inability to reflect the complexity and heterogeneity of human tumours

  • Patient-derived tumour xenograft models (PDTX), where surgically resected tumour samples are engrafted directly into immune-compromised mice, offer several advantages over standard cell-line xenograft models

  • PDTX tumours maintain the molecular, genetic and histological heterogeneity typical of tumours of origin through serial passaging in mice

  • The tumour histology of PDTX models provides an excellent in vivo preclinical platform to study cancer stem-cell biology and stromal–tumour interactions; novel cancer therapeutics can also be assessed

  • Well-characterized PDTX models represent an information-rich preclinical resource for analysis of drug activity, including novel–novel drug combinations, as well as predictive biomarker discovery

  • The PDTX approach to modelling of specific cancer types could potentially reduce non-informative animal studies while providing a more-relevant system to test clinically directed hypotheses

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Figure 1: Establishment and testing of PDTX models.
Figure 2: Comparison of genome-wide gene-expression profiles between primary patient tumours and PDTX tumours.
Figure 3: Predictive biomarker development strategy in PDTX models.

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  1. Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado, Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, 80045, CO, USA

    John J. Tentler, Aik Choon Tan, Colin D. Weekes, Antonio Jimeno, Stephen Leong, Todd M. Pitts, John J. Arcaroli, Wells A. Messersmith & S. Gail Eckhardt

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  1. John J. Tentler
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  2. Aik Choon Tan
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  3. Colin D. Weekes
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  4. Antonio Jimeno
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  5. Stephen Leong
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  6. Todd M. Pitts
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  7. John J. Arcaroli
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  8. Wells A. Messersmith
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  9. S. Gail Eckhardt
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All authors contributed equally to all aspects of the article, including researching data, discussion of content, writing, reviewing and editing the manuscript before submission.

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Correspondence to S. Gail Eckhardt.

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The authors declare no competing financial interests.

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Tentler, J., Tan, A., Weekes, C. et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol 9, 338–350 (2012). https://doi.org/10.1038/nrclinonc.2012.61

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