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Telomerase as a therapeutic target in glioblastoma
Elisa Aquilanti1,2, Lauren Kageler2, Patrick Y Wen1
1Division of Neuro Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Abstract:
Glioblastoma is the most common primary malignant brain tumor in adults and it continues to have a dismal prognosis. The development of targeted therapeutics has been particularly challenging, in part due to a limited number of oncogenic mutations and significant intra-tumoral heterogeneity. TERT promoter mutations were first discovered in melanoma and later found to be present in up to 80% of glioblastoma samples. They are also frequent clonal alterations in this tumor. TERT promoter mutations are one of the mechanisms for telomerase reactivation, providing cancers with cellular immortality. Telomerase is a reverse transcriptase ribonucleoprotein complex that maintains telomere length in cells with high proliferative ability. In this article, we present genomic and pre-clinical data that support telomerase as a potential "Achilles' heel" for glioblastoma. We also summarize prior experience with anti-telomerase agents and potential new approaches to tackle this target.
Insights
Glioblastoma, a deadly brain cancer, often has TERT promoter mutations that enable cell immortality via telomerase. Targeting telomerase may offer a new therapeutic strategy for glioblastoma treatment.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Glioblastoma is the most common primary malignant brain tumor with a poor prognosis.
- Targeted therapy development is hindered by limited oncogenic mutations and tumor heterogeneity.
- TERT promoter mutations are prevalent in glioblastoma, contributing to cellular immortality.
Purpose of the Study:
- To present genomic and pre-clinical data supporting telomerase as a therapeutic target in glioblastoma.
- To review existing anti-telomerase agents and explore novel therapeutic approaches.
Main Methods:
- Genomic analysis of glioblastoma samples.
- Pre-clinical evaluation of telomerase as a therapeutic target.
- Review of existing literature on anti-telomerase agents.
Main Results:
- TERT promoter mutations are frequent in glioblastoma and are linked to telomerase reactivation.
- Telomerase activity is crucial for maintaining telomere length and cellular immortality in glioblastoma.
- Genomic and pre-clinical data suggest telomerase is a viable therapeutic target.
Conclusions:
- Telomerase represents a potential "Achilles' heel" for glioblastoma treatment.
- Targeting telomerase reactivation, driven by TERT promoter mutations, could offer a novel therapeutic strategy.
- Further investigation into anti-telomerase agents is warranted for glioblastoma therapy.
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