文章：

基于细胞系的平台评估候选抗癌药物的治疗效果

Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents

原文发布日期：2010-03-19

DOI: 10.1038/nrc2820

类型: Review Article

开放获取: 否

要点：

1. Human tumour-derived cell lines have historically had a very important role in the discovery and development of new cancer therapeutics.
2. The National Cancer Institute 60 (NCI60) platform, which introduced the concept of high-throughput cell-based profiling, was crucial not only to the development of technologies that are still being used in various high-throughput discovery platforms, but also to the discovery of several agents that have subsequently been found to demonstrate therapeutic efficacy.
3. Subsequently developed genomic analysis technologies have provided an opportunity to link variable treatment responses to specific underlying genotypes, highlighting the enormous genomic heterogeneity in human cancer and its role in the response to therapy, and revealing the need to reconsider the scale of cell line-based studies to assess the activity of candidate anticancer agents.
4. Consequently, much larger panels of cancer cell lines are beginning to be exploited for the purpose of identifying genomic determinants of drug sensitivity, and several studies have validated the usefulness of this approach to reveal clinically informative biomarkers.
5. This development, together with additional technological developments involving various three-dimensional culture systems and more sophisticated xenograft models, has recently reinvigoratedthe application of cancer cell lines to the analysis of drug efficacy in cancer.
6. Although throughput, as well as the physiological relevance of some of these approaches, remains a limitation of these systems, there seems to be little doubt that tumour-derived cell lines will continue to have a vital role in the preclinical assessment of new candidate anticancer agents.

要点翻译：

1. 人类肿瘤源性细胞系在历史上对于新型癌症治疗方法的发现和开发具有极其重要的作用。
2. 引入高通量细胞分析理念的美国国家癌症研究所NCI60平台不仅对开发至今仍广泛应用于各类高通量发现平台的技术至关重要，还助力发现了数种后续被证实具有疗效的药物。
3. 随后发展的基因组分析技术为将可变治疗反应与特定潜在基因型关联提供了契机，既揭示了人类癌症巨大的基因组异质性及其在治疗应答中的作用，也促使我们重新审视基于细胞系的抗癌候选药物活性评估的研究规模。
4. 因此，为识别药物敏感性的基因组决定因素，规模更大的癌细胞系组合正开始被开发利用，多项研究也验证了这种方法在揭示临床信息性生物标志物方面的实用性。
5. 这一进展，连同涉及多种三维培养系统和更复杂异种移植模型的技术突破，近期重新激发了癌细胞系在抗癌药物功效分析中的应用活力。
6. 尽管通量以及部分方法的生理相关性仍是这些系统的局限，但毫无疑问，肿瘤源性细胞系将继续在新颖抗癌候选药物的临床前评估中发挥关键作用。

英文摘要：

Efforts to discover new cancer drugs and predict their clinical activity are limited by the fact that laboratory models to test drug efficacy do not faithfully recapitulate this complex disease. One important model system for evaluating candidate anticancer agents is human tumour-derived cell lines. Although cultured cancer cells can exhibit distinct properties compared with their naturally growing counterparts, recent technologies that facilitate the parallel analysis of large panels of such lines, together with genomic technologies that define their genetic constitution, have revitalized efforts to use cancer cell lines to assess the clinical utility of new investigational cancer drugs and to discover predictive biomarkers.

摘要翻译： 

发现新抗癌药物并预测其临床活性的努力受到一个事实的限制：用于测试药物效力的实验室模型无法忠实地重现这种复杂疾病。一个重要的候选抗癌药物评估模型系统是人源肿瘤衍生细胞系。尽管培养的癌细胞与其自然生长的对应物相比可能表现出不同的特性，但最近的技术促进了对大量此类细胞系进行平行分析，同时结合基因组学技术定义其遗传构成，这些进展重新激发了利用癌细胞系来评估新研究性抗癌药物的临床效用以及发现预测性生物标志物的努力。

原文链接：

Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents