Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?

被引:17
作者
Burko, Pavel [1 ]
D'Amico, Giuseppa [1 ]
Miltykh, Ilia [2 ]
Scalia, Federica [1 ,3 ]
de Macario, Everly Conway [3 ,4 ]
Macario, Alberto J. L. [3 ,4 ]
Giglia, Giuseppe [4 ,5 ]
Cappello, Francesco [1 ,4 ]
Bavisotto, Celeste Caruso [1 ,4 ]
机构
[1] Univ Palermo, Dept Biomed Neurosci & Adv Diagnost BIND, Sect Human Anat, I-90133 Palermo, Italy
[2] Penza State Univ, Inst Med, Dept Human Anat, Penza 440026, Russia
[3] Univ Maryland, Inst Marine & Environm Technol IMET, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21202 USA
[4] Euro Mediterranean Inst Sci & Technol IEMEST, I-90139 Palermo, Italy
[5] Univ Palermo, Dept Biomed Neurosci & Adv Diagnost BIND, Sect Human Physiol, I-90133 Palermo, Italy
关键词
glioblastoma multiforme; radioresistance; extracellular vesicles; intercellular communication; stem cells; tumor heterogeneity; tumor microenvironment; hypoxia; metabolic reprogramming; chaperone system; non-coding RNA; DNA repair; theranostics; personalized medicine; CANCER STEM-CELLS; NEWLY-DIAGNOSED GLIOBLASTOMA; STRAND BREAK REPAIR; DRUG-DELIVERY SYSTEMS; DOMAIN-CONTAINING; 3A; GLIOMA-CELLS; RADIATION-RESISTANCE; TEMOZOLOMIDE RESISTANCE; VALPROIC ACID; INTRATUMOR HETEROGENEITY;
D O I
10.3390/ijms24054883
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:25
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