Haney Steven A
Wyeth Research, Department of Biological Technologies, 35 Cambridge Park Drive, Cambridge, MA 02140, USA.
Expert Opin Ther Targets. 2007 Nov;11(11):1429-41. doi: 10.1517/14728222.11.11.1429.
RNA interference (RNAi) screening for cancer drug target identification has been growing, in both the number of laboratories carrying out screens and in the scale of the screens themselves, from the first screens that were published a few years ago. This growth is directly related to the significant new insights into cancer cell biology that have been defined by relatively few studies. Recently, such screens have moved from general studies of cancer cell function (finding new mechanisms of malignancy and tumor suppression), to screens that explain the clinical problems, such as resistance to chemotherapeutics. In light of the progression observed in these published studies, it is now possible to consider how RNAi screening can be used to characterize other areas of cancer research that have been proposed to explain the development of clinical cancers. Examples include: oncogene addiction/oncogenic shock, cancer stem cells, lineage dependency and the epithelial-mesenchymal transition. RNAi screening can enable critical evaluations of both the roles of these concepts in tumor development and provide starting points for new therapeutic programs targeting emerging areas of cancer cell biology.
从几年前首次发表的筛选研究开始，用于癌症药物靶点鉴定的RNA干扰（RNAi）筛选在开展筛选的实验室数量以及筛选规模方面都在不断发展。这种增长与相对较少的研究所定义的对癌细胞生物学的重大新见解直接相关。最近，此类筛选已从对癌细胞功能的一般研究（寻找恶性肿瘤和肿瘤抑制的新机制），转向解释临床问题的筛选，如对化疗药物的耐药性。鉴于这些已发表研究中观察到的进展，现在可以考虑如何利用RNAi筛选来表征癌症研究的其他领域，这些领域已被提出来解释临床癌症的发展。例子包括：癌基因成瘾/致癌休克、癌症干细胞、谱系依赖性和上皮-间质转化。RNAi筛选能够对这些概念在肿瘤发展中的作用进行关键评估，并为针对癌细胞生物学新兴领域的新治疗方案提供起点。
