# Targeting Prostaglandin Receptor EP2 for Glioma and Associated Epilepsy

> **NIH NIH R21** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $228,000

## Abstract

PROJECT SUMMARY
Gliomas, the most common type of primary brain tumors, constitute a significant cause of epilepsy, particularly
among the elderly. Current standard treatment, surgical resection followed by radiotherapy and chemotherapy
with temozolomide, merely provides a limited increase of median survival. As the leading presenting symptom
of malignant brain tumors, seizures often recur and aggravate during the course of illness. Despite the high
frequency of incidence, seizures caused by gliomas are poorly managed, as nearly 50% of patients show
resistance to current antiepileptic drugs (AEDs) and status epilepticus (SE) has been reported in more than 10%
of all malignant glioma cases. Refractory epilepsy represents a major impediment to tumor management;
therefore, there is a dire need for new therapies with sufficient efficacy for glioma patients who also suffer from
uncontrollable seizures. However, the molecular mechanisms of epileptogenesis in malignant tumor-bearing
brains are poorly understood. Recent evidence suggests that cyclooxygenase-2 (COX-2), a likely contributor to
some forms of acquired epilepsy, might be involved in the development of malignant gliomas via producing
prostaglandin E2 (PGE2). We show that PGE2 facilitates tumor cell proliferation, invasion and inflammation
largely through the Gαs-coupled EP2 receptor, and that activation of EP2 aggravates neuronal inflammation
and degeneration after prolonged seizures in epileptic rodents. Our main hypothesis is that blocking the
inflammatory prostaglandin receptor EP2 will impair the development of gliomas and thus suppress the
concomitant seizures. To test this hypothesis, we will use a combination of pharmacological and genetic
approaches to delineate the PGE2/EP2 signaling-mediated inflammation in human malignant glioma cells (Aim
1), and to determine the effects of EP2 receptor inhibition on the development of spontaneous seizures
associated with malignant gliomas (Aim 2). Successful completion of this project will lead to the identification of
novel molecular targets for the prevention and/or modification strategy for malignant gliomas and the
concomitant epilepsy.

## Key facts

- **NIH application ID:** 9841467
- **Project number:** 5R21NS109687-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Jianxiong Jiang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,000
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841467

## Citation

> US National Institutes of Health, RePORTER application 9841467, Targeting Prostaglandin Receptor EP2 for Glioma and Associated Epilepsy (5R21NS109687-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9841467. Licensed CC0.

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