{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:34:13Z","timestamp":1790775253830,"version":"4.1.0"},"reference-count":271,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms24054883","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T02:27:25Z","timestamp":1677810445000},"page":"4883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1344-9654","authenticated-orcid":false,"given":"Pavel","family":"Burko","sequence":"first","affiliation":[{"name":"Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2131-563X","authenticated-orcid":false,"given":"Giuseppa","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9130-3255","authenticated-orcid":false,"given":"Ilia","family":"Miltykh","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Institute of Medicine, Penza State University, 440026 Penza, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Scalia","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy"},{"name":"Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD 21202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everly","family":"Conway de Macario","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD 21202, USA"},{"name":"Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-2876","authenticated-orcid":false,"given":"Alberto J. L.","family":"Macario","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD 21202, USA"},{"name":"Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5616-3595","authenticated-orcid":false,"given":"Giuseppe","family":"Giglia","sequence":"additional","affiliation":[{"name":"Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy"},{"name":"Section of Human Physiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9288-1148","authenticated-orcid":false,"given":"Francesco","family":"Cappello","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy"},{"name":"Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-8471","authenticated-orcid":false,"given":"Celeste","family":"Caruso Bavisotto","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy"},{"name":"Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref_1","first-page":"3","article-title":"Glioblastoma Multiforme: A Review of Its Epidemiology and Pathogenesis through Clinical Presentation and Treatment","volume":"18","author":"Hanif","year":"2017","journal-title":"Asian Pac. 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