Trakoonsenathong R, Chiu CF, Saengboonmee C. Glucagon-like peptide 1 receptor agonist: A potential game changer for cholangiocarcinoma. World J Gastroenterol 2024; 30(34): 3862-3867 [PMID: 39350782 DOI: 10.3748/wjg.v30.i34.3862]
Corresponding Author of This Article
Charupong Saengboonmee, MD, PhD, Assistant Professor, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mittraphap Highway, Khon Kaen 40002, Thailand. charusa@kku.ac.th
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ronnakrit Trakoonsenathong, Charupong Saengboonmee, Cho-Kalaphruek Excellent Research Project for Medical Students, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Ronnakrit Trakoonsenathong, Charupong Saengboonmee, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Ronnakrit Trakoonsenathong, Charupong Saengboonmee, Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Ronnakrit Trakoonsenathong, Ching-Feng Chiu, Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 11031, Taiwan
Author contributions: Trakoonsenathong R and Saengboonmee C conceptualized, reviewed, outlined, and wrote the first draft of the manuscript; Chiu CF and Saengboonmee C discussed and revised the manuscript; All authors reviewed and approved the final version of the manuscript.
Supported by Mekong - Lancang Cooperation Special Fund; Cho-Kalaphruek Excellent Research Project for Medical Students; and The International Internship Pilot Program, No. IIPP2023283.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Charupong Saengboonmee, MD, PhD, Assistant Professor, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mittraphap Highway, Khon Kaen 40002, Thailand. charusa@kku.ac.th
Received: May 26, 2024 Revised: August 19, 2024 Accepted: August 27, 2024 Published online: September 14, 2024 Processing time: 106 Days and 23.9 Hours
Abstract
Glucagon-like peptide-1 receptor (GLP-1R) agonist, a subgroup of incretin-based anti-diabetic therapies, is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protection. Contrarily, concerns have been raised about GLP-1R agonists increasing the risk of particular cancers. Recently, several epidemiological studies reported contradictory findings of incretin-based therapy on the risk modification for cholangiocarcinoma (CCA). The first cohort study demonstrated that incretin-based therapy was associated with an increased risk of CCA. Later studies, however, showed a null effect of incretin-based therapy on CCA risk for dipeptidyl peptidase-4 inhibitor nor GLP-1R agonist. Mechanistically, glucagon-like peptide 1 receptor is multifunctional, including promoting cell growth. High GLP-1R expressions were associated with progressive phenotypes of CCA cells in vitro. Unexpectedly, the GLP-1R agonist showed anti-tumor effects on CCA cells in vitro and in vivo with unclear mechanisms. Our recent report also showed that GLP-1R agonists suppressed the expression of GLP-1R in CCA cells in vitro and in vivo, leading to the inhibition of CCA tumor growth. This editorial reviews recent evidence, discusses the potential effects of GLP-1R agonists in CCA patients, and proposes underlying mechanisms that would benefit from further basic and clinical investigation.
Core Tip: Glucagon-like peptide 1 receptor (GLP-1R) agonists, an anti-diabetic drug with other systemic benefits, have been reported for their association with increased risk of some cancers. Although the associations between GLP-1R agonists and the risk of cholangiocarcinoma (CCA) have not been consensus, the use of GLP-1R agonists showed the anti-tumor effects against CCA in vitro and animal models are evident. This editorial reviews and discusses recent studies of the effects of GLP-1R agonists both at epidemiological and molecular levels. The understanding of how GLP-1R agonist affects CCA will be beneficial for the management of patients with CCA and diabetes mellitus.
