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In Vitro Approach to Identify Preclinical Drug Targets to Treat Glioblastoma Multiforme

AJAS · 2025 Biomedical and Health Sciences (inferred)

Samvrit Rao · Virginia Academy of Science

Overview

Glioblastoma multiforme (GBM) is a highly malignant and prevalent form of brain cancer that continues to be largely incurable despite advancements in treatment modalities. The 2-year survival rate for individuals afflicted with GBM is approximately 18%. Recent studies have revealed that intercellular communication channels, known as Tunneling Nanotubes (TNTs), play a crucial role in the progression of GBM by facilitating the transfer of tumorigenic materials, thereby rendering the tumor resistant to treatment. The primary goal of my research project was to identify novel molecular drug targets using in vitro-aided computational approaches to prevent the transfer of tumorigenic cargo through TNTs between treatment-resistant and naive healthy cells to achieve GBM remission. Glioblastoma stem cells from autopsy tissue were cultured with naive astrocytes, laser microdissected to analyze TNTs, and omics-aided pathway analysis was performed to identify a key molecular drug target, JMJD8 (Jumonji domain containing 8), which was confirmed through Western Blot and Immunohistochemistry. Further, computational analysis using the Tumor Cancer Genomic Atlas database revealed that the drug Paclitaxel alters expression of JMJD8 through secondary mediators, inferring that it can be repurposed to target TNTs. In-vitro studies further validated this finding, demonstrating that Paclitaxel has significant impact on growth kinetics of cells isolated from aggressive GBM tumors. Additionally, by computationally reverse engineering the search using chemotherapeutic agents known to alter cell-to-cell communication, such as Vinblastine and Cytochalasin, as anchors, 5 possible novel modifiable drug targets were identified. In summary, this study identifies a key molecular drug target, JMJD8; demonstrates that Paclitaxel could be repurposed to achieve GBM tumor remission; and brings to attention 5 additional molecular targets. These novel drug targets and repurposed drugs can potentially alter GBM tumor progression and increase survival.

Competition history

  • AJAS 2025 Category not listed

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Source: AAAS Annual Meeting (Confex) / American Junior Academy of Science

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