Expanding the repertoire of RNA interference screens for developing new anticancer drug targets

Abstract

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.

Keywords::

• cancer
• oncology
• RNA interference screening
• small hairpin RNA
• small interfering RNA
• target validation