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PMID: 22508028 Published · epublish English Journal Article Review

Patient-derived tumour xenografts as models for oncology drug development.

Nature reviews. Clinical oncology ·Vol. 9 ·No. 6 ·2012-04-17 ·Pages 338-50

Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, Arcaroli JJ, Messersmith WA, Eckhardt SG

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.

MeSH Terms
Animals Antineoplastic Agents/therapeutic use Drug Design Humans Mice Neoplasms/drug therapy Xenograft Model Antitumor Assays
Chemicals
Antineoplastic Agents
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Tentler John J
Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO 80045, USA.
Tan Aik Choon
Weekes Colin D
Jimeno Antonio
Leong Stephen
Pitts Todd M
Arcaroli John J
Messersmith Wells A
Eckhardt S Gail
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Article Info
Journal
Nature reviews. Clinical oncology
Abbr.
Nat Rev Clin Oncol
ISSN
1759-4782
DOI
10.1038/nrclinonc.2012.61
Published
2012-04-17
Epub
2012-00-17
Pages
338-50
Language
English
Region
England
NLM ID
101500077
PMCID
PMC3928688
Subset
IM
Grants
NCI NIH HHS · P30 CA046934 · United States
External Links
PubMed source DOI: 10.1038/nrclinonc.2012.61 PMC Full Text View journal details
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