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Potential use of RNA interference in cancer therapy

Published online by Cambridge University Press:  18 August 2010

Connor Phalon
Affiliation:
Gradalis, Inc., Dallas, TX, USA.
Donald D. Rao
Affiliation:
Gradalis, Inc., Dallas, TX, USA.
John Nemunaitis*
Affiliation:
Gradalis, Inc., Dallas, TX, USA. Mary Crowley Cancer Research Centers, Dallas, TX, USA. Texas Oncology PA, Dallas, TX, USA. Baylor Sammons Cancer Center, Dallas, TX, USA.
*
*Corresponding author: John Nemunaitis, 1700 Pacific Ave, Suite 1100, Dallas, TX 75201, USA. E-mail: [email protected]

Abstract

RNA interference (RNAi) is an evolutionary conserved mechanism for specific gene silencing. This mechanism has great potential for use in targeted cancer therapy. Understanding the RNAi mechanism has led to the development of several novel RNAi-based therapeutic approaches currently in the early phases of clinical trials. It remains difficult to effectively deliver the nucleic acids required in vivo to initiate RNAi, and intense effort is under way in developing effective and targeted systemic delivery systems for RNAi. Description of in vivo delivery systems is not the focus of this review. In this review, we cover the rationale for pursuing personalised cancer therapy with RNAi, briefly review the mechanism of each major RNAi therapeutic technique, summarise and sample recent results with animal models applying RNAi for cancer, and provide an update on current clinical trials with RNAi-based therapeutic agents for cancer therapy. RNAi-based cancer therapy is still in its infancy, and there are numerous obstacles and issues that need to be resolved before its application in personalised therapy focusing on patient-cancer-specific targets can become standard cancer treatment, either alone or in combination with other treatments.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2010

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References

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Further reading, resources and contacts

Hannon, G.J. (2002) RNA interference. Nature 418, 244-251CrossRefGoogle ScholarPubMed
Bild, A.H. et al. (2006) Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 439, 353-357CrossRefGoogle ScholarPubMed
Fire, A. et al. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811CrossRefGoogle ScholarPubMed
Devi, G.R. (2006) siRNA-based approaches in cancer therapy. Cancer Gene Therapy 13, 819-829CrossRefGoogle ScholarPubMed