Extrahepatic cytochrome P450 epoxygenases: pathophysiology and clinical significance in human gastrointestinal cancers

Abstract

Cytochrome P450 (CYP) epoxygenases, a multi-gene superfamily of hemecontaining enzymes, are commonly known to metabolize endogenous arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs). The role of CYPs is mostly studied in liver drugs metabolism, cardiac pathophysiology, and hypertension fields. Particularly, the biological functions of these enzymes have increasingly attracted a growing interest in cancer biology. Most published studies on CYPs in cancer have been limited to their role as drug metabolizing systems. The activity of these enzymes may affect drug pharmacokinetics and bioavailability as well as exogenous compounds turnover. Some CYP isoforms are selectively highly expressed in tumors, suggesting a potential mechanistic role in promoting resistance to chemotherapy. Majority of drugs elicit their effects in extrahepatic tissues whereby their metabolism can significantly determine treatment outcome. Nonetheless, the role of extrahepatic CYPs is not fully understood and targeting these enzymes as effective anti-cancer therapies are yet to be developed. This review article summarizes an up-to-date body of information from published studies on CYP enzymes expression levels and pathophysiological functions in human normal and malignant gastrointestinal (GI) tract tissues. Specifically, we reviewed and discussed the current research initiatives by emphasizing on the clinical significance and the pathological implication of CYPs in GI malignancies of esophagus, stomach, and colon.

The Analysis of Potential Diagnostic and Therapeutic Targets for the Occurrence and Development of Gastric Cancer Based on Bioinformatics

“…Overall, few studies have been conducted on intragastric CYPs, possibly because the expression of CYPs is generally lower in the normal gastric mucosa than in other parts of the gastrointestinal tract, and the role of CYPs in driving gastric carcinogenesis remains largely unknown. Also, more studies are needed to understand the potential significance of CYPs in gastric cancer [33]. Expression and prognosis analysis showed that the expression level of 12 core genes was significantly changed in gastric cancer compared with normal gastric tissues.…”

Meta-Analysis on the Improvement of Symptoms and Prognosis of Gastrointestinal Tumors Based on Medical Care and Exercise Intervention

“…Among them, each sample point is composed of instance X and label Y, with instance X � (x (1) , x (2) 10,11]. e empirical risk of model f(x, w) is expressed as…”

“…Pidkovka et al believe that targeted therapy has changed the treatment model for diseases, but the clinical effect on gastrointestinal malignancies is relatively low. Although their research has a positive effect on the follow-up treatment of patients, it lacks necessary experimental data [2]. Feng et al believe that the nonopioid analgesic Analgin is used to treat acute and chronic pain and fever.…”