RNA interference-based therapies against brain tumors: Potential clinical strategies

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.