title: Patient-derived tumour xenografts as models for oncology drug development.
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.
authors.affiliation: Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO 80045, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Tentler
authors.forename: Aik Choon
authors.initials: AC
authors.lastname: Tan
authors.forename: Colin D
authors.initials: CD
authors.lastname: Weekes
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
authors.forename: Stephen
authors.initials: S
authors.lastname: Leong
authors.forename: Todd M
authors.initials: TM
authors.lastname: Pitts
authors.forename: John J
authors.initials: JJ
authors.lastname: Arcaroli
authors.forename: Wells A
authors.initials: WA
authors.lastname: Messersmith
authors.forename: S Gail
authors.initials: SG
authors.lastname: Eckhardt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents