{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:26:35Z","timestamp":1791919595545,"version":"4.3.4"},"reference-count":124,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Glioblastoma (GB) is the most common and most aggressive primary brain tumor in adults, with an overall survival almost 14.6 months. Optimal resection followed by combined temozolomide chemotherapy and radiotherapy, also known as Stupp protocol, remains the standard of treatment; nevertheless, resistance to temozolomide, which can be obtained throughout many molecular pathways, is still an unsurpassed obstacle. Several factors influence the efficacy of temozolomide, including the involvement of other DNA repair systems, aberrant signaling pathways, autophagy, epigenetic modifications, microRNAs, and extracellular vesicle production. The blood\u2013brain barrier, which serves as both a physical and biochemical obstacle, the tumor microenvironment\u2019s pro-cancerogenic and immunosuppressive nature, and tumor-specific characteristics such as volume and antigen expression, are the subject of ongoing investigation. In this review, preclinical and clinical data about temozolomide resistance acquisition and possible ways to overcome chemoresistance, or to treat gliomas without restoration of chemosensitinity, are evaluated and presented. The objective is to offer a thorough examination of the clinically significant molecular mechanisms and their intricate interrelationships, with the aim of enhancing understanding to combat resistance to TMZ more effectively.<\/jats:p>","DOI":"10.3390\/life14060673","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T05:36:06Z","timestamp":1716528966000},"page":"673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Overcoming Resistance to Temozolomide in Glioblastoma: A Scoping Review of Preclinical and Clinical Data"],"prefix":"10.3390","volume":"14","author":[{"given":"Dimitra","family":"Smerdi","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Second Department of Internal Medicine, \u201cAttikon\u201d University General Hospital, Athens Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9314-3187","authenticated-orcid":false,"given":"Myrto","family":"Moutafi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Second Department of Internal Medicine, \u201cAttikon\u201d University General Hospital, Athens Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Kotsantis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Second Department of Internal Medicine, \u201cAttikon\u201d University General Hospital, Athens Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lampis C.","family":"Stavrinou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurotraumatology, \u201cAttikon\u201d University General Hospital, Athens Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Psyrri","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Second Department of Internal Medicine, \u201cAttikon\u201d University General Hospital, Athens Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.drudis.2015.02.011","article-title":"Toward an effective strategy in glioblastoma treatment. 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