Targeting Cyclins and Cyclin-dependent Kinases Involved in Cell Cycle Regulation by RNAi as a Potential Cancer Therapy
The cell cycle is a complex, tightly regulated process of cell division. The deregulation of the cell cycle that leads to unscheduled proliferation of cells is the main hallmark of cancer. Cell cycle defects are often mediated by alterations in the activity of cyclins and cyclin-dependent kinases (CDKs) in hyper-proliferative cancer cells. Although several chemical inhibitors that target cyclins and CDKs have been developed and screened at the clinical stage as anticancer agents, none of these inhibitors have been approved as therapeutic agents. Therefore an alternative strategy will be beneficial to decrease the expression of unregulated cyclins and CDKs, and RNA interference (RNAi) has emerged as an effective approach in recent years to silence the expression of cell cycle proteins in order to control malignant cell growth. In this chapter, we focus on the use of RNAi which can target and silence expression of cyclins and CDKs in order to realize a clinical benefit in cancer therapy. We review current studies on silencing cyclins and CDKs, with special emphasis on the use of synthetic carriers and delivery systems to achieve effective silencing. Critical factors that contribute to the efficiency of RNAi have been highlighted to bring this therapeutic approach to the clinical realm.