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Published on: June 2, 2020
Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular
Pavel Burko1, Giuseppa D'Amico1, Ilia Miltykh2
1Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy.
Abstract:
Glioblastoma multiforme (GBM) is a primary brain tumor that is very aggressive, resistant to treatment, and characterized by a high degree of anaplasia and proliferation. Routine treatment includes ablative surgery, chemotherapy, and radiotherapy. However, GMB rapidly relapses and develops radioresistance. Here, we briefly review the mechanisms underpinning radioresistance and discuss research to stop it and install anti-tumor defenses. Factors that participate in radioresistance are varied and include stem cells, tumor heterogeneity, tumor microenvironment, hypoxia, metabolic reprogramming, the chaperone system, non-coding RNAs, DNA repair, and extracellular vesicles (EVs). We direct our attention toward EVs because they are emerging as promising candidates as diagnostic and prognostication tools and as the basis for developing nanodevices for delivering anti-cancer agents directly into the tumor mass. EVs are relatively easy to obtain and manipulate to endow them with the desired anti-cancer properties and to administer them using minimally invasive procedures. Thus, isolating EVs from a GBM patient, supplying them with the necessary anti-cancer agent and the capability of recognizing a specified tissue-cell target, and reinjecting them into the original donor appears, at this time, as a reachable objective of personalized medicine.
Insights
Glioblastoma multiforme (GBM) is an aggressive brain tumor resistant to therapy. Extracellular vesicles (EVs) show promise for diagnosing GBM and delivering targeted anti-cancer treatments, offering a personalized medicine approach.
Area of Science:
- Neuro-oncology
- Nanomedicine
- Cancer Biology
Background:
- Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with high rates of relapse and resistance to standard treatments like surgery, chemotherapy, and radiotherapy.
- Mechanisms of radioresistance in GBM are complex and multifactorial, involving cellular and microenvironmental factors.
Purpose of the Study:
- To review the mechanisms contributing to GBM radioresistance.
- To explore the potential of extracellular vesicles (EVs) in overcoming treatment resistance and developing novel therapeutic strategies for GBM.
Main Methods:
- Review of existing literature on GBM radioresistance mechanisms.
- Focus on the role of extracellular vesicles (EVs) as diagnostic tools and drug delivery vehicles.
Main Results:
- Multiple factors contribute to GBM radioresistance, including stem cells, tumor heterogeneity, microenvironment, hypoxia, metabolic reprogramming, chaperone systems, non-coding RNAs, DNA repair, and EVs.
- EVs are identified as promising candidates for GBM diagnostics, prognostics, and targeted therapy delivery due to their ease of manipulation and administration.
Conclusions:
- Extracellular vesicles (EVs) offer a versatile platform for personalized medicine in GBM treatment.
- Targeted delivery of anti-cancer agents via engineered EVs represents a feasible strategy for combating GBM recurrence and resistance.
