The Evolving Relationship: Impact of Combined Radiotherapy and Temozolomide Treatment on Critical Biomarkers in Glioblastoma Multiforme Patients; A Comprehensive Analysis
https://doi.org/10.22034/thr.2025.236676
Babak Olia, Feruza Ruzimova, Atajanov Adilbek Yuldashevich, Madrimov Javoxir Islombek o'g'li, Niginabonu Khajiqurbonova, Fayzullayev Umidjon O‘Ktamovich, Xudoynazarova Dilnura, Jalolbek Doschanov, Mahdi Hazratgholi
Abstract 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.