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. 2016 Oct 4;7(40):66212-66225.
doi: 10.18632/oncotarget.11184.

Patient-derived xenograft models of colorectal cancer in pre-clinical research: a systematic review

Kai M Brown  1   2   3 , Aiqun Xue  3 , Anubhav Mittal  1   2   3 , Jaswinder S Samra  1   2 , Ross Smith  3 , Thomas J Hugh  1   2   3
Affiliations

Patient-derived xenograft models of colorectal cancer in pre-clinical research: a systematic review

Kai M Brown et al. Oncotarget. .

Abstract

Aims: We sought to objectively assess the internal and external validity of patient-derived xenograft (PDX) models as a platform in pre-clinical research into colorectal cancer (CRC). Metastatic disease is the most common cause of death from CRC, and despite significant research, the results of current combination chemotherapy and targeted therapies have been underwhelming for most of this patient group. One of the key factors limiting the success of translational CRC research is the biologically inaccurate models in which new therapies are developed.

Methods: We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist and SYRCLE (Systematic Review Centre for Laboratory animal Experimentation) guidelines to search Ovid MEDLINE and Embase databases up to July 2015 to identify studies involving PDX models of CRC where the model had been validated across multiple parameters. Data was extracted including host mouse strain, engraftment rate, site of engraftment, donor tumour source and development of metastases in the model.

Results: Thirteen articles satisfied the inclusion criteria. There was significant heterogeneity amongst the included studies, but overall the median engraftment rate was high (70%) and PDX models faithfully recapitulated the characteristics of their patient tumours on the microscopic, genetic and functional levels.

Conclusions: PDX models of CRC have a reasonable internal validity and a high external validity. Developments in xenografting technology are broadening the applications of the PDX platform. However, the included studies could be improved by standardising reporting standards and closed following the ARRIVE (Animals in Research: Reporting In Vivo Experiments) guidelines.

Keywords: PDX; animal model; colorectal cancer; patient-derived xenograft; systematic review.

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Conflict of interest statement

CONFLICTS OF INTEREST

None to disclose.

Figures

Figure 1
Figure 1. PRISMA Flow Chart
Figure 2
Figure 2. PDX Models of CRC; cumulative number of publications by application and by year of publication
See this image and copyright information in PMC

References

    1. Australian Institute of Health and Welfare . Canberra: 2010. Cancer in Australia 2010: an overview. Dec. Report No.: Cancer series no. 60. Available from http://www.aihw.gov.au/publication-detail/?id=6442472459.
    1. GLOBOCAN. International Agency for Research on Cancer Colorectal Cancer Estimated Incidence, Mortality and Prevalence Worldwide in 2012. 2012 [cited 2014 Sep 21]. Available 2014 Sep 21, from http://globocaniarcfr/Pages/fact_sheets_canceraspx.
    1. Renouf DJ, Woods R, Speers C, Hay J, Phang PT, Fitzgerald C, Kennecke H. Improvements in 5-year outcomes of stage II/III rectal cancer relative to colon cancer. Am J Clin Oncol. 2013;36:558–64. doi: 10.1097/COC.0b013e318256f5dc. - DOI - PubMed
    1. Sargent D, Sobrero A, Grothey A, O'Connell MJ, Buyse M, Andre T, Zheng Y, Green E, Labianca R, O'Callaghan C, Seitz JF, Francini G, Haller D, et al. Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2009;27:872–7. doi: 10.1200/JCO.2008.19.5362. - DOI - PMC - PubMed
    1. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383:1490–502. doi: 10.1016/S0140-6736(13)61649-9. - DOI - PubMed

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