Current views on inducing synthetic lethal RNAi responses in the treatment of cancer.
Cancer cells arise from normal cells that have incurred mutations in oncogenes and tumor suppressor genes. The mutations are often unique and not readily found in normal cells, giving rise to the opportunity of exploiting these mutations to induce synthetic lethality. Synthetic lethality occurs when inhibition or mutation in two or more separate genes leads to cell death while inhibition or mutations of either gene alone has no lethal effect on the cell. Using RNA interference (RNAi) to identify synthetic lethality has become a growingly popular screening approach. Areas covered: In this review, we cover the use of RNAi therapeutics to induce synthetic lethality in cancer. Additionally, we discuss several select small molecule inhibitors that were identified or verified by RNAi that induce synthetic lethality in specific cancers. We also discuss the identification of novel synthetic lethal combinations and the cancer model that the combination was validated in. Lastly, we discuss RNAi delivery vehicles. Expert opinion: While RNAi therapeutics have great potential to treat cancer, due to the siRNA delivery problem, RNAi remains more commonly used as a tool, rather than a therapeutic. However, with emerging technological advances in the field of RNAi therapeutics, it is only a matter of time before RNAi-induced synthetic lethal clinical studies are initiated in cancer patients.