Translational Oncology Research Centre, Cancer Laboratory, Pathology Centre - Level F, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK.
Curr Opin Pharmacol. 2010 Aug;10(4):375-9. doi: 10.1016/j.coph.2010.05.001.
The discovery of anti-cancer drugs has become dependent on cell lines, which are used to screen potential compounds for activity as well as to explore cancer biology. Cell lines produce rapid results, but their relevance to patient outcomes is questionable as they undergo selection over many passages to a point where they are no longer representative of their originating tumour. This has led to the increasing use of primary cell cultures, primary tumour cell explants, early passage cell lines, and xenografts to improve the accuracy of results during drug development. Over the last few years, there has been an increasing interest in these methods and they are now firmly established, with a plethora of different techniques available. For instance, explant and three-dimensional models allow cell:cell interactions to be examined in live cells, and endpoints can include the measurement of gene expression and image analysis. In the future, anti-cancer drug development is likely to use a combination of molecular, cell line, primary or early passage cell culture, and xenograft methods for lead optimisation before clinical trials are contemplated.
抗癌药物的发现已经越来越依赖于细胞系，这些细胞系被用于筛选潜在的具有活性的化合物，以及探索癌症生物学。细胞系能够快速产生结果，但它们与患者预后的相关性值得怀疑，因为它们在经过多次传代后会发生选择，以至于不再能代表其起源肿瘤。这导致越来越多地使用原代细胞培养物、原代肿瘤细胞外植体、早期传代细胞系和异种移植物来提高药物开发过程中结果的准确性。在过去几年中，人们对这些方法越来越感兴趣，它们现在已经得到了充分的确立，并且有大量不同的技术可供选择。例如，外植体和三维模型允许在活细胞中检查细胞间的相互作用，终点可以包括基因表达的测量和图像分析。在未来，抗癌药物的开发可能会在临床试验之前，综合使用分子、细胞系、原代或早期传代细胞培养物和异种移植物方法，以优化先导化合物。
