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MicroRNAs in Cancer Translational Research pp 533–549Cite as

RNAi-based Approaches to the Treatment of Brain Tumors

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Abstract

The discovery of RNA interference (RNAi) as an alternate mode of gene regulation utilized by eukaryotes has greatly expanded the arsenal of molecular tools that a biomedical researcher can employ to target tumors. Thus, it will be natural to extend this methodology from bench to the bedside as a novel mode of clinical intervention against intracranial tumors, as these are frequently refractive to conventional therapies, i.e. surgery, radiotherapy, and chemotherapy. Induction of RNAi in the targeted tumor can be multifaceted, with two primary modes of therapeutic intervention postulated to date; delivery of in silico designed and in vitro synthesized non-coding RNA molecules to the tumor, or the pharmacological perturbation of non-coding RNA molecules that are endogenously expressed by the tumor. Both modes silence gene expression, but via somewhat different molecular pathways. Two key non-coding RNA molecules that are known to impart RNAi are small interfering RNA and microRNA. Both are currently under investigation in pre-clinical and clinical settings for their potential utility against tumors, with small interfering RNA already proving their efficacy in several small-scale clinical trials. However, despite demonstration of excellent potential as an anti-cancer therapy at the bench, the current inability to deliver therapeutically significant levels of RNAi into the diseased tissue remains a primary hurdle that needs to be overcome for widespread utility at the bedside. This chapter presents an update on both the latest methodologies that have been utilized for induction of RNAi in brain tumors, both in pre-clinical and clinical settings, as well as descriptions of the molecular pathways that have been targeted via RNAi. The pioneering RNAi-based clinical trials that have been tested against brain tumors are also described to illustrate both the utility and the impact of this novel mode of brain tumor therapy at the bedside.

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Acknowledgments

Research support for S.P. Mathupala 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. Sloan 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, Detroit, MI, 48201, USA

    Saroj P. Mathupala, Sandeep Mittal & Murali Guthikonda

  2. Department of Neurological Surgery, Case Comprehensive Cancer Center, Case Medical Center, University Hospitals, Cleveland, OH, 44106, USA

    Andrew E. Sloan

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  1. Saroj P. Mathupala
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Correspondence to Saroj P. Mathupala .

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  1. , Department of Clinical Oncology, Queen Elizabeth Hospital, Gascoigne Road 30, Hong Kong SAR, China, People's Republic

    William C.S. Cho

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Mathupala, S.P., Mittal, S., Guthikonda, M., Sloan, A.E. (2011). RNAi-based Approaches to the Treatment of Brain Tumors. In: Cho, W. (eds) MicroRNAs in Cancer Translational Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0298-1_22

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