Enhancing reproducibility in cancer drug screening: how do we move forward?
Enhancing reproducibility in cancer drug screening: how do we move forward?
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DOI：
10.1158/0008-5472.can-14-0725
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发表时间：
2014-08-01
期刊：
影响因子：
11.2
通讯作者：
Haibe-Kains B
中科院分区：
文献类型：
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作者：
Hatzis C;Bedard PL;Birkbak NJ;Beck AH;Aerts HJ;Stem DF;Shi L;Clarke R;Quackenbush J;Haibe-Kains B
大规模的药物基因组学高通量筛选（HTS）研究在产生药物反应的稳健基因组预测因子方面具有巨大潜力。最近的两项大规模HTS研究报告了此类筛选的结果，揭示了几种已知和新型药物敏感性和生物标志物。然而，随后的评价发现，药物应答表型的实验室间一致性仅为中度，这可能是由于两项研究中使用的实验方案存在差异。这突出表明，需要在社区范围内实施标准化检测，以测量药物反应表型，从而实现HTS的全部潜力。我们建议，前进的道路是通过集体努力建立这些测定中关键步骤的最佳实践和标准化，以确保大规模筛选产生的数据不仅具有高的研究内一致性，而且可以在多个实验室中成功复制和比较。药物基因组学高通量筛选为靶向治疗的合理开发提供了巨大的希望，但除非通过集体努力使实验方案和分析方法标准化，否则其全部潜力将无法实现。
Large-scale pharmacogenomic high throughput screening (HTS) studies hold great potential for generating robust genomic predictors of drug response. Two recent large-scale HTS studies have reported results of such screens, revealing several known and novel drug sensitivities and biomarkers. Subsequent evaluation however found only moderate inter-laboratory concordance in the drug response phenotypes, possibly due to differences in the experimental protocols used in the two studies. This highlights the need for community-wide implementation of standardized assays for measuring drug response phenotypes so that the full potential of HTS is realized. We suggest that the path forward is to establish best practices and standardization of the critical steps in these assays through a collective effort to ensure that the data produced from large-scale screens would not only be of high intra-study consistency, so that they could be replicated and compared successfully across multiple laboratories. Pharmacogenomic high throughput screening offers tremendous promise in the rational development of targeted therapies, but its full potential will not be realized unless experimental protocols and analysis methods are standardized through a collective effort.