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

Nataliya Pidkovka, Olena Rachkevych and Abbes Belkhiri _

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Oncotarget. 2021; 12:379-391. https://doi.org/10.18632/oncotarget.27893

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Nataliya Pidkovka1, Olena Rachkevych2 and Abbes Belkhiri3,4

1 Department of Health Science, South College, Nashville, TN, USA

2 Department of Obstetrics and Gynecology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

3 Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

4 Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

Correspondence to:

Abbes Belkhiri,email: [email protected]

Keywords: cytochrome P450 epoxygenases; extrahepatic CYPs; gastrointestinal cancers; epoxyeicosatrienoic acids; arachidonic acid

Received: December 23, 2020     Accepted: February 01, 2021     Published: February 16, 2021

Copyright: © 2021 Pidkovka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Cytochrome P450 (CYP) epoxygenases, a multi-gene superfamily of heme-containing 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.

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