Mazandaran Association of Emergency Medicine Translational Health Reports 3092-6750 2 1 2025 12 20 The Evolving Relationship: Impact of Combined Radiotherapy and Temozolomide Treatment on Critical Biomarkers in Glioblastoma Multiforme Patients; A Comprehensive Analysis 236676 10.22034/thr.2025.236676 EN Babak Olia Department of Radiology, Faculty of Veterinary Medicine, Science and Research Branch, Tehran, Iran Feruza Ruzimova Department of Pedagogy and psychology , Urgench state university, Urgench, Uzbekistan Atajanov Adilbek Yuldashevich Department Of General Science , Mamun University,Khiv, Uzbekistan Madrimov Javoxir Islombek O'g'li Department of Medicine , Urgench Mamun University  Urgench , Uzbekistan. Niginabonu Khajiqurbonova Department of clinical subjects , Tashkent State Medical University  Tashkent, Uzbekistan Fayzullayev Umidjon O‘Ktamovich Department of Psychology, Mamun university, Khiva Uzbekistan Xudoynazarova Dilnura Department of Psychology, Mamun university, Khiva, Uzbekistan Jalolbek Doschanov Department of Pedagogy and Primary Education Methodology,Urgench Innovation University , Urgench, Uzbekistan. Mahdi Hazratgholi Department of Radiology, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran 0009-0004-0851-3588 Journal Article Background: The established first-line treatment for newly diagnosed Glioblastoma Multiforme (GBM) involves maximal surgical removal of the tumor, followed by a regimen of radiotherapy (RT) together with concurrent and maintenance temozolomide (TMZ) chemotherapy. Patient response to this combined approach varies widely and is closely associated with the tumor's molecular characteristics. Objective: This analysis compiles current research on how the RT/TMZ combination modifies crucial GBM biomarkers over time, focusing on therapy-induced alterations rather than their initial prognostic significance. Methods: A systematic review of literature from January 2000 to July 2024 was performed using PubMed, Scopus, and Web of Science. Search keywords included "glioblastoma," "radiotherapy," "temozolomide," "MGMT," "IDH," "biomarker," and related terms. Emphasis was placed on clinical trials and key preclinical studies. Results: The RT/TMZ protocol imposes significant selective pressure, dynamically influencing GBM biomarkers. MGMT promoter methylation is the primary predictor of TMZ efficacy, but treatment often leads to the expansion of MGMT-active, resistant tumor clones at recurrence. IDH1/2 mutations are strong prognostic indicators, and their associated metabolic changes may increase tumor sensitivity to DNA-damaging therapies. Treatment substantially reshapes the tumor immune microenvironment; RT can stimulate anti-tumor immune responses but also increase PD-L1 expression, while TMZ often causes severe lymphocyte depletion. Additionally, therapy promotes the selection of cells with enhanced DNA damage repair mechanisms and activates survival pathways such as EGFR, fostering treatment resistance. Conclusion: RT and TMZ induce continuous, adaptive changes in GBM biomarkers. Recognizing this dynamic process is essential for personalizing treatment, assessing response, and developing new combination therapies to combat resistance.

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