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Updated: Feb 23, 2026
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
RNA interference for glioblastoma therapy: Innovation ladder from the bench to clinical trials
Eunice L Lozada-Delgado1, Nilmary Grafals-Ruiz2, Pablo E Vivas-Mejía3
1Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00927, United States; Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00935, United States; Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00935, United States.
Abstract:
Glioblastoma multiforme (GBM) is the most common and deadliest type of primary brain tumor with a prognosis of 14months 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 oligonucleotides 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.
Insights
RNA interference (RNAi) shows promise for treating glioblastoma multiforme (GBM). Overcoming delivery challenges, like crossing the blood-brain barrier, is key for RNAi therapy to become a reality for brain tumor patients.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Biotechnology
Background:
- Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with poor prognosis despite current multimodal treatments.
- Limited improvement in overall survival for GBM patients over the past two decades necessitates novel therapeutic strategies.
- RNA interference (RNAi) offers a post-transcriptional gene regulation approach with potential for cancer therapy, including GBM.
Purpose of the Study:
- To review the translational progress of RNA interference (RNAi)-based therapies for glioblastoma multiforme (GBM).
- To connect in vitro findings with pre-clinical evidence for RNAi in GBM treatment.
- To identify key challenges and potential solutions for advancing RNAi therapy for GBM.
Main Methods:
- Delineation of RNAi effects in GBM cell lines.
- Assessment of RNAi efficacy in preclinical glioma mouse models.
- Comparison of drug delivery systems for transporting RNAi molecules across the blood-brain barrier (BBB).
Main Results:
- RNAi demonstrates therapeutic potential in GBM cell lines and glioma models.
- Systemic limitations such as poor circulatory stability and low tumor tissue release hinder RNAi efficacy.
- Efficient delivery across the blood-brain barrier remains a significant hurdle for brain tumor targeting.
Conclusions:
- RNAi-based therapies hold significant promise for glioblastoma treatment.
- Overcoming challenges in stability, tumor delivery, and blood-brain barrier penetration is crucial for clinical translation.
- Further development of drug carriers and delivery strategies is essential for realizing the potential of RNAi in GBM therapy.
