Synthetic lethal genetic screens in Ras mutant cancers

Abstract

Mutations in the Ras family of small GTPases are among the most frequent oncogenic events in human cancer. Difficulties in targeting Ras itself and the limited efficacy in targeting its effector kinases have spurred the search for Ras synthetic lethal genes that could shed new light on the biology of Ras-driven cancer and lead to new therapeutic strategies. Advances in mammalian RNAi technology have enabled high-throughput functional screens for Ras synthetic lethal interactions. In this chapter, we summarize the strategies and findings from these screens and discuss future improvement for Ras synthetic lethality studies.

Keywords: Non-oncogene addiction; RNAi screen; Synthetic lethality; shRNA; siRNA.