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Targeting Oncogenes with siRNAs

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siRNA and miRNA Gene Silencing

Part of the book series: Methods in Molecular Biology ((MIMB,volume 487))

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Abstract

Current cancer chemotherapies heavily rely on the unspecific inhibition of proliferating cells. This lack of tumour cell specificity results in severe toxic side effects and may only hardly affect quiescent cancer stem cells consequently leading to relapse. Since oncogenes are exclusively expressed in malignant and pre-malignant cells, they may provide unique, cancer cell specific targets for therapeutic strategies. However, their role in maintaining the malignant phenotype is frequently unknown. Furthermore, oncogenic transcription factors are generally considered to be “undruggable” with conventional small molecule approaches. Oncogene-specific RNA interference offers here new and exciting options to analyse oncogene functions directly in the malignant environment. Moreover, such approaches may permit the targeting of oncogenic transcription factors, thereby considerably extending the number of cancer-specific target structures. In this chapter, several rationales and practical aspects of oncogene targeting with siRNAs are discussed. Special emphasis is given to the application of RNA interference to haematopoietic cells, which are generally hard to transfect. In particular, solving the problem of systemic siRNA/shRNA delivery will greatly advance the inclusion of RNA interference strategies into more efficient and specific therapeutic strategies.

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Acknowledgements

I wish to thank Simon Bomken for carefully reading the manuscript. I gratefully acknowledge support from the Deutsche Krebshilfe, the Deutsche Jose Carreras Leukaemie-Stiftung, the Wilhelm Sander-Stiftung and the North of England Children’s Cancer Research Fund.

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  1. Newcastle University, Northern Institute for Cancer Research, Paul O’Gorman Building, Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH

    Olaf Heidenreich

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  1. Olaf Heidenreich
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Correspondence to Olaf Heidenreich .

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  1. Institute for Cancer Research, Dept. Immunology, Norwegian Radium Hospital, Montebello, Oslo, 0310, Norway

    Mouldy Sioud

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Heidenreich , O. (2009). Targeting Oncogenes with siRNAs. In: Sioud, M. (eds) siRNA and miRNA Gene Silencing. Methods in Molecular Biology, vol 487. Humana Press. https://doi.org/10.1007/978-1-60327-547-7_11

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  • DOI: https://doi.org/10.1007/978-1-60327-547-7_11

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