Dissecting cancer pathways and vulnerabilities with RNAi

The latest generation of molecular-targeted cancer therapeutics has bolstered the notion that a better understanding of the networks governing cancer pathogenesis can be translated into substantial clinical benefits. However, functional annotation exists for only a small proportion of genes in the human genome, raising the likelihood that many cancer-relevant genes and potential drug targets await identification. Unbiased genetic screens in invertebrate organisms have provided substantial insights into signaling networks underlying many cellular and organismal processes. However, such approaches in mammalian cells have been limited by the lack of genetic tools. The emergence of RNA interference (RNAi) as a mechanism to suppress gene expression has revolutionized genetics in mammalian cells and has begun to facilitate decoding of gene functions on a genome scale. Here, we discuss the application of such RNAi-based genetic approaches to elucidating cancer-signaling networks and uncovering cancer vulnerabilities.