Prospects of RNA interference therapy for cancer

Abstract

RNA interference (RNAi) is a powerful gene-silencing process that holds great promise in the field of cancer therapy. The discovery of RNAi has generated enthusiasm within the scientific community, not only because it has been used to rapidly identify key molecules involved in many disease processes including cancer, but also because RNAi has the potential to be translated into a technology with major therapeutic applications. Our evolving understanding of the molecular pathways important for carcinogenesis has created opportunities for cancer therapy employing RNAi technology to target the key molecules within these pathways. Many gene products involved in carcinogenesis have already been explored as targets for RNAi intervention, and RNAi targeting of molecules crucial for tumor-host interactions and tumor resistance to chemo- or radiotherapy has also been investigated. In most of these studies, the silencing of critical gene products by RNAi technology has generated significant antiproliferative and/or proapoptotic effects in cell-culture systems or in preclinical animal models. Nevertheless, significant obstacles, such as in vivo delivery, incomplete suppression of target genes, nonspecific immune responses and the so-called off-target effects, need to be overcome before this technology can be successfully translated into the clinical arena. Significant progress has already been made in addressing some of these issues, and it is foreseen that early phase clinical trials will be initiated in the very near future.

MSP58 Knockdown Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo

“…RNA interference (RNAi) is a widespread and powerful tool used for the functional regulation of gene expression, and it has been developed as a potential therapeutic strategy in various diseases, including cancers (Pai et al, 2006;Boudreau et al, 2012). However, the knockdown effect of regular synthesized siRNA only lasts for a short time and does not allow the stable inhibition of target gene function.…”

Studies on the inhibition of feline EGFR in squamous cell carcinoma: Enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors

“…29,30 In this study gefitinib effectively reduced cellular migration and proliferation in the feline SCC cell line, but at the relatively typically transient in nature, with observed effects lasting up to one week. 24 To investigate if longer term knockdown of the receptor could be achieved, the siRNA sequence was cloned into a hairpin expression vector. Transfection efficiencies achieved with the hairpin transfection vectors were lower than what was achieved with the naked siRNA transfections (53 vs. 69% for vector and siRNA transfections respectively, data not shown).…”

“…22,23 RNA interference (RNAi) is a highly specific method of gene silencing which utilizes small interfering RNA (siRNA) molecules complementary to the target sequence. 24 These bind to gene transcripts targeting them for early destruction before translation can occur. 24 RNA interference techniques are extensively used in research but also carry promise for the development of drugs capable of targeting specific proteins 25,26 including EGFR.…”

“…24 These bind to gene transcripts targeting them for early destruction before translation can occur. 24 RNA interference techniques are extensively used in research but also carry promise for the development of drugs capable of targeting specific proteins 25,26 including EGFR. 27 The aims of this study were to investigate the role of EGFR in feline SCCs.…”

Suppression of Cellular Apoptosis Susceptibility (CSE1L) Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells

“…Therefore, CSE1L may present a potential molecular target in colon cancer therapy RNA silencing or as known as RNA interferences (RNAi) has been demonstrated to be highly effective and promising in the field of cancer therapy (Castanotto and Rossi, 2009). The two main strategies are delivery of chemically synthesized RNAi (non-viral delivery), or delivery of short hairpin RNA (shRNA)-encoding genes by engineered viruses that will ultimately generate RNAi by transcription in the target cells (Pai et al, 2005). Up to now, many gene products involved in carcinogenesis have already been explored as targets for RNAi.…”