# Epitranscriptome Associated with Glioblastoma Therapeutic Resistance

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $450,875

## Abstract

Gliomas account for about 60% of all primary central nervous system tumors. Glioblastoma (GBM or grade IV
glioma), which comprises 51.2% of all gliomas, is the most malignant form. Over the last two decades, the major
breakthrough in the treatment for GBM has been the addition of the DNA alkylating agent temozolomide (TMZ)
to the standard of care. Nevertheless, 90% of patients receiving both TMZ and radiation die after 5 years, a
colossal failure that has partially attributed to drug resistance. At the cellular level, ribonucleic acid (RNA) plays
a central role in many cellular processes and serves as structural components. In comparison to the modification
of genomic DNA, cellular RNAs are less protected and more prone to be modified by chemical or enzymatic
reactions within the cell. Up to date, there are 74 known RNA modifications in eukaryotic cells. Some RNA
modifications are essential for normal cellular activities, such as folding of tRNA molecules, however, depending
on their positions, the same RNA modification can have the opposite effect. The epitranscriptome is further
complicated by the concurrent activities of writers and erasers of RNA modifications. Overall, the dynamic in
epitranscriptome is expected to hold one of the keys to our health. We hypothesize that the variations in GBM
epitranscriptome plays an important role in TMZ resistance. Using accurate mass spectrometric method to detect
RNA modifications, we aim to validate the association of specific epitranscriptomic profile with TMZ resistance
in GBM using both in vitro and in vivo patient-xenograft models. Further, we will use different experimental
approaches to study the role of epitranscriptome in the development of TMZ resistance in GBM. Finally, we will
attempt to unravel the target associated with TMZ-resistance specific mRNA modification and will evaluate them
as a potential target for GBM adjuvant therapy in combination with TMZ. Overall, we expect to categorize the
role of RNA modifications associated with TMZ resistance, thus further enhance our understanding on the role
of epitranscriptome in the development of chemotherapeutic resistance in GBM.

## Key facts

- **NIH application ID:** 10072992
- **Project number:** 1R21NS118917-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Norman H. L. Chiu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,875
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072992

## Citation

> US National Institutes of Health, RePORTER application 10072992, Epitranscriptome Associated with Glioblastoma Therapeutic Resistance (1R21NS118917-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072992. Licensed CC0.

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