期刊
LIFE SCIENCES
卷 188, 期 -, 页码 26-36出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2017.08.027
关键词
RNAi; Glioblastoma; GBM; Nanoparticles; Mouse models
资金
- University of Puerto Rico Comprehensive Cancer Center (PEVM)
- Center for Collaborative Research in Health Disparities (RCMI) Grant [G12 MD007600]
- National Institutes of Health, Minority Biomedical Research Support (MBRS) RISE Grant [R25GM061838]
Glioblastoma multiforme (GBM) is the most common and deadliest type of primary brain tumor with a prognosis of 14 months after diagnosis. Current treatment for GBM patients includes total tumor resection, temozolomide-based chemotherapy, radiotherapy or a combination of these options. Although, several targeted therapies, gene therapy, and immunotherapy are currently in the clinic and/or in clinical trials, the overall survival of GBM patients has hardly improved over the last two decades. Therefore, novel multitarget modalities are urgently needed. Recently, RNA interference (RNAi) has emerged as a novel strategy for the treatment of most cancers, including GBM. RNAi-based therapies consist of using small RNA oligonudeotides to regulate protein expression at the post-transcriptional level. Despite the therapeutic potential of RNAi molecules, systemic limitations including short circulatory stability and low release into the tumor tissue have halted their progress to the clinic. The effective delivery of RNAi molecules through the blood-brain barrier (BBB) represents an additional challenge. This review focuses on connecting the translational process of RNAi-based therapies from in vitro evidence to pre-clinical studies. We delineate the effect of RNAi in GBM cell lines, describe their effectiveness in glioma mouse models, and compare the proposed drug carriers for the effective transport of RNAi molecules through the BBB to reach the tumor in the brain. Furthermore, we summarize the most important obstacles to overcome before RNAi-based therapy becomes a reality for GBM treatment.
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