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Patient-derived xenograft models of colorectal cancer in pre-clinical research: a systematic review
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Abstract
Kai M. Brown1,2,3, Aiqun Xue3, Anubhav Mittal1,2,3, Jaswinder S. Samra1,2, Ross Smith3 and Thomas J. Hugh1,2,3
1 Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia
2 Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, New South Wales, Australia
3 Cancer Surgery and Metabolism Research Group, The Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Correspondence to:
Kai M. Brown, email:
Keywords: patient-derived xenograft, colorectal cancer, systematic review, PDX, animal model
Received: February 07, 2016 Accepted: July 18, 2016 Published: August 10, 2016
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.
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