title: Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies.
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.
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: Stacey
authors: S
authors: Bagby
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: Wells A
authors: WA
authors: Messersmith
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: Todd M
authors: TM
authors: Pitts
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: Anna
authors: A
authors: Capasso
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: Marileila
authors: M
authors: Varella-Garcia
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: Peter J
authors: PJ
authors: Klauck
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: Jihye
authors: J
authors: Kim
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: Aik-Choon
authors: AC
authors: Tan
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: S Gail
authors: SG
authors: Eckhardt
authors: Medicine, University of Colorado Denver Anschutz Medical Campus.
authors: John J
authors: JJ
authors: Tentler
authors: Medicine, University of Colorado Denver Anschutz Medical Campus; john.arcaroli@ucdenver.edu.
authors: John
authors: J
authors: Arcaroli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D055808:Drug Discovery; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009369:Neoplasms; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents