# Prevention of obesity-enhanced colorectal cancer via targeting soluble epoxide hydrolase

> **NIH NIH R03** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2020 · $73,098

## Abstract

Project Summary
It is well established that obese individuals have increased risks of developing colorectal cancer (CRC),
however, the mechanism by which obesity increases the risks of CRC are not well understood and there are
few effective strategies to prevent obesity-enhanced CRC. The objective of our research is to determine the
roles of soluble epoxide hydroalse (sEH) in obesity-enhanced CRC and to establish an effecitve strategy for
prevention of obesity-enhanced CRC using sEH inhibitors that are currently being evaluated in multiple human
clinical trials. Our recent publication (PNAS 2018) shows that sEH and its metabolic products are over-
expressed in colon of obese mice; in addition, pharmacological inhibition or genetic ablation of sEH abolishes
obesity-induced colonic inflammation and activation of pro-tumorigenic Wnt signaling, which are early events
involved in the carcinogenesis of CRC and play critical roles in initiation and promotion of CRC. Considering
the essential roles of colonic inflammation and Wnt signaling in the carcinogenesis of CRC, in this project we
will test our hypothesis that genetic ablation or pharmacological inhibition of soluble epoxide hydrolase (sEH)
attenuates obesity-enhanced colorectal cancer (CRC). To test this hypothesis, we propose two specific aims:
(1) compare the development of obesity-enhanced azoxymethane (AOM)-induced CRC in sEH-/- and wild-type
(WT) mice, and (2) determine the effect of a drug candidate GSK2256294, which is a potent, selective, and
reversible sEH inhibitor and has been demonstrated to be safe from human clinical trials, on obesity-enhanced
AOM-induced CRC in mice.

## Key facts

- **NIH application ID:** 10021621
- **Project number:** 5R03CA237795-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Eric Decker
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $73,098
- **Award type:** 5
- **Project period:** 2019-09-23 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021621

## Citation

> US National Institutes of Health, RePORTER application 10021621, Prevention of obesity-enhanced colorectal cancer via targeting soluble epoxide hydrolase (5R03CA237795-02). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10021621. Licensed CC0.

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