# CYCLOOXYGENASE-2 SIGNALING IN CELL SENESCENCE AND ITS ROLE IN CHEMOTHERAPY-INDUCED LONG-TERM ADVERSE SEQUELAE

> **NIH NIH R15** · MIDWESTERN UNIVERSITY (GLENDALE AZ) · 2020 · $450,000

## Abstract

PROJECT SUMMARY
Survivors of childhood cancer are often associated with adverse, late-onset side effects of earlier cancer
treatments, which can be severe or even life-threatening. However, the underlying mechanisms of therapy-
induced late effects in this growing population are not known. We developed a novel mouse model for the late
effects of chemotherapy, in which juvenile exposure to doxorubicin (DOX) results in tissue accumulation of
senescent cells in adult mice and persistent up-regulation of cyclooxygenase-2 (COX2), a key enzyme in
prostanoid synthesis. Using this model, we found that treatment with aspirin, a COX inhibitor, following juvenile
exposure to DOX improved the long-term adverse effects and reduced the levels of senescent markers in adult
mice. Additionally, we have recently reported that inducible expression of COX2 in adult transgenic mice led to
increased senescence and a panel of early-aging phenotypes. Given the suggested role of cellular senescence
in side effects of chemotherapy, we hypothesize that COX2 plays an important role in chemotherapy-induced
senescence and that targeting the prostanoid signaling can effectively suppress senescence. Specific Aim 1
will establish COX2 as a mediator of chemotherapy-induced senescence using a novel mouse model and
define its mechanism. In Specific Aim 2, we aim to identify the prostanoid signaling as a better and more
selective therapeutic target for cellular senescence. Completion of the proposed research will identify potential
treatment strategies to prevent the long-term adverse effects of childhood cancer therapies, which will lead to a
higher quality of survivorship. At the same time, it could provide a novel insight into the role of COX2 in normal
and pathological aging processes.

## Key facts

- **NIH application ID:** 9880178
- **Project number:** 1R15CA246429-01
- **Recipient organization:** MIDWESTERN UNIVERSITY (GLENDALE AZ)
- **Principal Investigator:** Minsub Shim
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,000
- **Award type:** 1
- **Project period:** 2019-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880178

## Citation

> US National Institutes of Health, RePORTER application 9880178, CYCLOOXYGENASE-2 SIGNALING IN CELL SENESCENCE AND ITS ROLE IN CHEMOTHERAPY-INDUCED LONG-TERM ADVERSE SEQUELAE (1R15CA246429-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9880178. Licensed CC0.

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