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.
Keywords
- Epidermal Growth Factor Receptor
- Brain Tumor
- Glioma Cell Line
- Malignant Brain Tumor
- Formyl Peptide Receptor
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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- 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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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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