Development and maintenance of a preclinical patient derived tumor xenograft model for the investigation of novel anti-cancer therapies

Stacey Bagby, Wells A. Messersmith, Todd M. Pitts, Anna Capasso, Marileila Varella-Garcia, Peterj Klauck, Jihye Kim, Aik-Choon Tan, S. Gail Eckhardt, John J. Tentler, John Arcaroli

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5 Citations (Scopus)

Abstract

Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor pieces are injected subcutaneously into athymic nude mice (immunocompromised, T cell deficient) to create a bank of tumors and subsequently are passaged into different generations of mice in order to maintain these tumors from patients. Importantly, cellular heterogeneity of the original tumor is closely emulated in this model, which provides a more clinically relevant model for evaluation of drug efficacy studies (single agent and combination), biomarker analysis, resistant pathways and cancer stem cell biology. Some limitations of the PDTX model include the replacement of the human stroma with mouse stroma after the first generation in mice, inability to investigate treatment effects on metastasis due to the subcutaneous injections of the tumors, and the lack of evaluation of immunotherapies due to the use of immunocompromised mice. However, even with these limitations, the PDTX model provides a powerful preclinical platform in the drug discovery process.

Original languageEnglish
Article numbere54393
JournalJournal of Visualized Experiments
Volume2016
Issue number115
DOIs
Publication statusPublished - 2016 Sep 30
Externally publishedYes

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Keywords

  • Cancer research
  • CRC
  • Heterogeneity
  • Issue 115
  • PDTX
  • Preclinical
  • Stroma
  • Tumor bank

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bagby, S., Messersmith, W. A., Pitts, T. M., Capasso, A., Varella-Garcia, M., Klauck, P., Kim, J., Tan, A-C., Eckhardt, S. G., Tentler, J. J., & Arcaroli, J. (2016). Development and maintenance of a preclinical patient derived tumor xenograft model for the investigation of novel anti-cancer therapies. Journal of Visualized Experiments, 2016(115), [e54393]. https://doi.org/10.3791/54393