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RNA Interference-Based Therapies Against Brain Tumors: Potential Clinical Strategies

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Therapeutic Ribonucleic Acids in Brain Tumors

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Abstract

Harnessing the transcriptional pathway as a “master-switch” for re-profiling of aberrant signaling and metabolic cascades of tumors provides a novel mode of clinical intervention, particularly against neoplasms that are refractive to standard therapies. Brain tumors are prime candidates for new modes of therapy, as conventional therapies including surgical intervention, radiotherapy, and chemotherapy fare poorly against them. Two potent molecular techniques are available for interfering with a tumor's transcriptional machinery, i.e., small interfering RNA (siRNA), designed and administered exogenously, and microRNA (miRNA), an endogenous, self-regulated cellular repertoire of molecules that impart a tertiary level of gene regulation above and over the influence of classical signal transduction pathways. Both RNAi moieties are currently being examined in preclinical settings for their potential utility against malignant gliomas in future clinical applications. In this chapter, we will examine the glioma-specific cellular strategies that are presented for targeting via both siRNA and miRNA. Current progress in brain tumor-directed targeting of therapeutic amounts of RNAi, including those developed for traversing the blood–brain barrier will also be discussed. The challenges that need to be overcome in utilizing miRNA in a future clinical strategy against glioma, and imaging techniques under development for visualizing RNAi delivery will also be addressed.

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Abbreviations

siRNA:

Short interfering RNA

shRNA:

Short-hairpin RNA

miRNA:

MicroRNA

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Acknowledgements

Research support for the corresponding author (S.P.M.) was provided by a grant from the National Cancer Institute/National Institute of Health (CA 116257), the Fund for Medical Research and Education (FMRE), Wayne State University, and a gift from the Marvin E. Klein, M.D., Charitable Trust. A.E.S. is supported by grants from the National Cancer Institute/National Institute of Health (KO8 101954) and the Case Western Reserve University School of Medicine.

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Authors and Affiliations

  1. Department of Neurological Surgery, Karmanos Cancer Institute, Wayne State University, School of Medicine, 607 HWCRC, 4100 John R. Road, Detroit, MI, 48201, USA

    Saroj P. Mathupala, Sandeep Mittal & Murali Guthikonda

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  1. Saroj P. Mathupala
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  2. Sandeep Mittal
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  3. Murali Guthikonda
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  4. Andrew E. Sloan
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Correspondence to Saroj P. Mathupala .

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Editors and Affiliations

  1. Inst. Chemie und Biochemie, FU Berlin, Thielallee 63, Berlin, 14195, Germany

    Volker A. Erdmann

  2. Inst. Neuropathologie, Universitätsklinikum Düsseldorf, Moorenstr. 5, Düsseldorf, 40225, Germany

    Guido Reifenberger

  3. Inst. Bioorganic Chemistry, PAN Poznan, ul. Z. Noskowskiego 12/14, Poznan, 61-704, Poland

    Jan Barciszewski

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Mathupala, S.P., Mittal, S., Guthikonda, M., Sloan, A.E. (2009). RNA Interference-Based Therapies Against Brain Tumors: Potential Clinical Strategies. In: Erdmann, V., Reifenberger, G., Barciszewski, J. (eds) Therapeutic Ribonucleic Acids in Brain Tumors. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00475-9_14

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