[RNA interference for cancer therapies]

Abstract

RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing in mammalian cells and its discovery has lead to its wide application as a powerful tool in post-genomic research. Recently, short interfering RNA (siRNA), which induces RNAi, has been experimentally introduced as a cancer therapy and is expected to be developed as a nucleic acid-based medicine. Selection of appropriate gene targets is an important parameter in the potential success of siRNA cancer therapies. Candidate targets include genes associated with cell proliferation, metastasis, angiogenesis, and drug resistance. Importantly, silencing of such genes must not affect the functions of normal cells. Development of suitable drug delivery systems (DDSs) is also an important issue. Numerous methods to transfect siRNAs into cells have been developed, and the use of non-viral DDSs is preferred because it offers greater safety for clinical application than does the use of viral DDSs. In this article, we briefly review the mechanism of RNAi and non-viral DDSs. Next, we discuss some of the most recent findings concerning the administration of siRNAs against polo-like kinase-1 (PLK-1), which regulates the mitotic process in mammalian cells. Finally, several current clinical trials of RNAi therapies against cancers are discussed. Results of current studies and clinical trials demonstrate that manipulation of the RNAi mechanism by use of targeted siRNA offers a novel and attractive therapeutic option against cancer.