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Potential microRNA therapies targeting Ras , NF B and p 53 signaling

Introduction Developing therapeutics that target cell survival and death promoting signals is an intense area of focus in cancer research. Various studies conducted over multiple decades have demonstrated that tumors arise from misregulated signaling events that control the equilibrium between cell survival and death [1]. Alterations, which are frequently genomic mutations in the soma or germline, often lead to the activation of oncogenic proteins, such as Ras or NF B, typically concomitantly with the inhibition of tumor suppressors, the most notable of which is p53. In this altered state, cells gain the ability to grow and proliferate irrepressibly, leading to tumorigenesis. Successful attempts have been made to reduce uncontrollable cell growth by interfering with the Ras [2-4] and NF B [5-8] survival pathways, and/or introducing or reactivating p53 [4,9-15]. These preclinical and clinical studies suggest that targeting these pathways may represent one strategy toward the treatment of cancer. Nevertheless, additional approaches