Cytochrome P450 monooxygenase/soluble epoxide hydrolase-mediated eicosanoid pathway in colorectal cancer and obesity-associated colorectal cancer.

Jianan Zhang,Guodong Zhang,Katherine Z Sanidad

doi:10.18632/oncoscience.488

Jianan Zhang, Guodong Zhang + Show 1 more

Open Access

https://doi.org/10.18632/oncoscience.488

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Journal: Oncoscience	Publication Date: Aug 23, 2019
Citations: 5	License type: CC BY 3.0

Affiliation: University of Massachusetts Amherst

Abstract

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States. Furthermore, it is well established that obese individuals have high risks of developing CRC, and obesity-associated CRC represents an unmet medical problem in the United States. Using a metabolomics approach, our recent research supports that the cytochrome P450 (CYP) monooxygenase/soluble epoxide hydrolase (sEH)-mediated eicosanoid pathway could play critical roles in the pathogenesis of CRC and obesity-associated CRC. Here in this review, we discuss recent studies about the roles of the CYP/sEH eicosanoid pathway in the pathogenesis of these diseases.

Highlights

In the United States, there are ~130,000 new cases and ~50,000 deaths caused by colorectal cancer (CRC) every year, making CRC a serious health problem [1]
Our results support that cytochrome P450 (CYP) monooxygenases could be potential therapeutic targets of CRC, since we showed that the inhibition or deletion of CYP monooxygenases suppresses colon tumorigenesis in mice [12]
Pharmacological inhibition or genetic ablation of soluble epoxide hydrolase (sEH) abolishes obesityinduced colonic inflammation and the activation of pro-tumorigenic Wnt signaling [41]. These results demonstrate that sEH is required for obesity-induced colonic inflammation and activation of Wnt signaling, which are early events involved in the carcinogenesis of CRC and play critical roles in the initiation and promotion of CRC [42, 43]. These findings support that sEH could be a novel therapeutic target of obesity-associated CRC; sEH inhibitors, which are currently being evaluated in clinical trials targeting other disorders [10, 11], could be promising agents for preventing obesity-associated CRC

Summary

Introduction

In the United States, there are ~130,000 new cases and ~50,000 deaths caused by colorectal cancer (CRC) every year, making CRC a serious health problem [1]. It is important to identify novel therapeutic targets of CRC in order to develop safe and effective approaches for prevention and/or treatment. Our recent research supports that the CYP monooxygenase pathway could play an important role in regulating the development of CRC [12].

Results

Conclusion