Synergistic Effects of TMZ and TERT Inhibition on TMZ-Resistant Glioblastomas
AJAS · 2025 Biomedical and Health Sciences (inferred)
Overview
Glioblastoma is the most common primary malignant brain tumor in adults and continues to have a median survival time of less than 15 months. Some glioblastomas are resistant to common radiosensitizers, such as temozolomide (TMZ), which are key components of chemoradiation therapy. Resistance may be linked to the expression of telomerase reverse transcriptase (TERT), a ribonucleoprotein complex that regulates telomere length in highly proliferative cells. TERT promoter mutations are found in up to 80% of glioblastomas and cause TERT reactivation that provides cancer with cellular immortality. TERT expression has also been linked to maintaining protectively low levels of intracellular reactive oxygen species. This study investigated the potential synergistic effects of TERT inhibition and TMZ therapy in the TMZ-resistant T98g cancer cell line. TERT inhibition was achieved by RNA interference, then telomere length was measured by qPCR, and cell viability and ROS measured by respective luminescence-based assays. The results here show that TERT inhibition increases intracellular ROS, decreases telomerase activity, and overall increases TMZ susceptibility. This work provides new insight into the role of TERT in combating chemotherapeutic drug resistance and will aid future studies to develop targeted treatments for glioblastoma.
Competition history
- AJAS 2025
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Source: AAAS Annual Meeting (Confex) / American Junior Academy of Science