Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?
Pavel BurkoGiuseppa D'AmicoIlia MiltykhFederica ScaliaEverly Conway de MacarioAlberto J L MacarioGiuseppe GigliaFrancesco CappelloC Caruso BavisottoPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- minimally invasive
- dna repair
- dna damage response
- stem cells
- single cell
- early stage
- locally advanced
- radiation therapy
- cell therapy
- cancer stem cells
- endothelial cells
- working memory
- squamous cell carcinoma
- signaling pathway
- single molecule
- bone marrow
- combination therapy
- surgical site infection
- smoking cessation
- robot assisted