1. ¹Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA
2. ²Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
3. ³Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA
4. ⁴Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
5. ⁵Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
6. ⁶Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Correspondence: Dr T-C Wu, Department of Pathology, Johns Hopkins University School of Medicine, Richard Ross Research Building, Room 512CD8, Ross 512H, 720 Rutland Avenue, Baltimore, MD 21205, USA. E-Mail: wutc@jhmi.edu

Received 2 August 2005; Revised 25 October 2005; Accepted 1 November 2005; Published online 8 December 2005.

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.