Patient-derived xenograft models of colorectal cancer in pre-clinical research: a systematic review.
Patient-derived xenograft models of colorectal cancer in pre-clinical research: a systematic review.
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DOI：
10.18632/oncotarget.11184
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发表时间：
2016-10-04
期刊：
影响因子：
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通讯作者：
Hugh TJ
中科院分区：
文献类型：
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作者：
Brown KM;Xue A;Mittal A;Samra JS;Smith R;Hugh TJ
我们试图客观评估患者来源的异种移植(PDX)模型作为结直肠癌(CRC)临床前研究平台的内部和外部有效性。转移性疾病是结直肠癌最常见的死亡原因，尽管有大量研究，但目前联合化疗和靶向治疗的结果对这一群体中的大多数人来说并不令人印象深刻。限制转化型结直肠癌研究成功的关键因素之一是生物学上不准确的模型，在这些模型中开发了新的治疗方法。我们使用PRISMA(系统评价和Meta分析的首选报告项目)核对表和SYRCLE(实验室动物实验系统评价中心)指南搜索截至2015年7月的Ovid MEDLINE和Embase数据库，以确定涉及PDX模型的结直肠癌研究，该研究的模型已在多个参数下得到验证。在模型中提取数据，包括宿主小鼠品系、植入率、植入位置、供体肿瘤来源和转移情况。13篇文章符合纳入标准。纳入的研究之间存在显著的异质性，但总体上中位数植入率很高(70%)，PDX模型在微观、遗传和功能水平上忠实地概括了患者肿瘤的特征。CRC的PDX模型具有合理的内部效度和较高的外部效度。异种移植技术的发展拓宽了PDX平台的应用范围。然而，纳入的研究可以通过标准化报告标准来改进，并遵循到达(研究中的动物：活体实验中的报告)指南关闭。
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. 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. 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. 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.