TARGETING SOX2 EXPRESSION IN GLIOBLASTOMA: INSIGHTS FROM COMPUTATIONAL ANALYSIS AND DRUG REPURPOSING

Abstract

Aim: This study aims to explore the potential of targeting SOX2, a critical transcription factor that contributes to the development of glioblastoma multiform (GBM), an extremely aggressive form of brain cancer. GBM poses a substantial obstacle because of its swift advancement and its resistance to standard therapies. Several transcription factors includingOCT4, NANOG, c MYC, and SOX2 are crucial for the onset and course of GBM. SOX2 is particularly notable as a potential target for therapeutic intervention because of its vital function in glioblastoma stem cells (GSCs) and its participation in cell proliferation, survival, and self-renewal mechanisms. The study primarily examines the levels of SOX2 expression in GBM by employing the GEPIA2 platform. GEPIA2 stands for Gene Expression Profiling Interactive Analysis 2, which allows for the investigation of gene expression patterns in different cancer subtypes. Using GEPIA2, the analysis of SOX2 expression in GBM can offer valuable information about its potential as a target for therapy and its association with disease advancement and patient results. This research is being conducted to determine if downregulating SOX2 expression could be a viable therapeutic strategy. The computational technique of molecular docking will be utilized to forecast the interaction between SOX2 and potential small molecule inhibitors or modulators. Additionally, the study seeks to investigate the concept of drug repurposing, which involves assessing the potential of existing drugs that have been approved for other uses to target SOX2 in GBM. Result: We have found that tumor cells express SOX2 at a higher level than normal cells. We used GEPIA2 to analyze the expression level of SOX2 and predict disease-free survival, and overall survival, and the expression level is compared to other genes and transcription factors (TFs) such as TP53, EGFR, PTEN, c-MYC, SOX2, and more. SOX2 expression level is higher than other TFs. We have identified several potential drugs, including Cosmegen, Niraparib, Penfluridol, Dastinib, Paapverin, etc., that effectively downregulate the expression of SOX2. Conclusion: SOX2 targeting is a potential treatment for GBM. Drug repurposing and molecular docking can identify drugs that overcome high SOX2 expression levels. These insights suggest a promising direction for cancer treatment research and development.