Oxysterols and gastrointestinal cancers around the clock
- 1Faculty of Medicine, University of Ljubljana, Slovenia
- 2Faculty of Ljubljana, University of Ljubljana, Slovenia
This review focuses on the role of oxidized sterols in three major gastrointestinal cancers (hepatocellular carcinoma, pancreatic and colon cancer) and how the circadian clock affects the carcinogenesis by regulating the lipid metabolism and beyond. While each field of research (cancer, oxysterols, and circadian clock) is well studied within their specialty, little is known about the intertwining mechanisms and how these influence the disease etiology in each cancer type. Oxysterols are involved in pathology of these cancers, but final conclusions about their protective or damaging effects are elusive, since the effect depends on the type of oxysterol, concentration and the cell type. Oxysterol concentrations, the expression of key regulators liver X receptors (LXR), farnesoid X receptor (FXR), and oxysterol-binding proteins (OSBP) family are modulated in tumors and plasma of cancer patients, exposing these proteins and selected oxysterols as new potential biomarkers and drug targets. Evidence about how cholesterol/oxysterol pathways are intertwined with circadian clock is building. Identified key contact points are different forms of retinoic acid receptor related orphan receptors (ROR) and LXRs. RORs and LXRs are both regulated by sterols/oxysterols and the circadian clock and in return also regulate the same pathways, representing a complex interplay between sterol metabolism and the clock. With this in mind, in addition to classical therapies to modulate cholesterol in gastrointestinal cancers, such as the statin therapy, the time is ripe also for therapies where time and duration of the drug application is taken as an important factor for successful therapies. The final goal is the personalized approach with chronotherapy for disease management and treatment in order to increase the positive drug effects
Keywords: oxysterols, Circadian Rhythm, Hepatocelular carcinoma (HCC), Pancreatic Cancer, colorectal cancer, Cholesterol, ROR, LXR, FXR, SREBP
Received: 08 Jan 2019;
Accepted: 03 Jul 2019.
Edited by:Vincenzo Pezzi, University of Calabria, Italy
Reviewed by:Carsten Carlberg, University of Eastern Finland, Finland
Jean-Marc A. Lobaccaro, Université Clermont Auvergne, France
Thomas Burris, Washington University in St. Louis, United States
Copyright: © 2019 Kovač, Skubic, Bohinc, Rozman and Rezen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Tadeja Rezen, University of Ljubljana, Faculty of Medicine, Ljubljana, 1000, Slovenia, firstname.lastname@example.org