Chu YD, Chen CW, Lai MW, Lim SN, Lin WR. Bioenergetic alteration in gastrointestinal cancers: The good, the bad and the ugly. World J Gastroenterol 2023; 29(29): 4499-4527 [PMID: 37621758 DOI: 10.3748/wjg.v29.i29.4499]
Corresponding Author of This Article
Wey-Ran Lin, AGAF, MD, PhD, Professor, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, No. 5 Fu-Shin Street, Taoyuan 333, Taiwan. t12360@adm.cgmh.org.tw
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
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/
World J Gastroenterol. Aug 7, 2023; 29(29): 4499-4527 Published online Aug 7, 2023. doi: 10.3748/wjg.v29.i29.4499
Bioenergetic alteration in gastrointestinal cancers: The good, the bad and the ugly
Yu-De Chu, Chun-Wei Chen, Ming-Wei Lai, Siew-Na Lim, Wey-Ran Lin
Yu-De Chu, Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Chun-Wei Chen, Wey-Ran Lin, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Ming-Wei Lai, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Siew-Na Lim, Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Wey-Ran Lin, Department of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Author contributions: Chu YD and Chen CW contributed equally to this article; Chu YD and Chen CW wrote the draft of the manuscript; Lai MW and Lim SN collected the data; Lin WR reviewed and edited the manuscript.
Supported byMinistry of Science and Technology, Taiwan, No. MOST-110-2314-B-182A-095- and No. MOST-111-2314-B-182A-126- (to Lin WR); and Chang Gung Memorial Hospital, Linkou Branch, Taiwan, No. CMRPG3K2292, No. CMRPG3J0693 (to Lin WR), No. CORPG3J0531, No. CORPG3L0261, No. CORPG3J0501, and No. CMRPG3K0771 (to Chen CW).
Conflict-of-interest statement: The authors declare no conflicts of interests.
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: Wey-Ran Lin, AGAF, MD, PhD, Professor, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, No. 5 Fu-Shin Street, Taoyuan 333, Taiwan. t12360@adm.cgmh.org.tw
Received: March 28, 2023 Peer-review started: March 28, 2023 First decision: May 12, 2023 Revised: May 23, 2023 Accepted: July 3, 2023 Article in press: July 3, 2023 Published online: August 7, 2023 Processing time: 126 Days and 9.6 Hours
Abstract
Cancer cells exhibit metabolic reprogramming and bioenergetic alteration, utilizing glucose fermentation for energy production, known as the Warburg effect. However, there are a lack of comprehensive reviews summarizing the metabolic reprogramming, bioenergetic alteration, and their oncogenetic links in gastrointestinal (GI) cancers. Furthermore, the efficacy and treatment potential of emerging anticancer drugs targeting these alterations in GI cancers require further evaluation. This review highlights the interplay between aerobic glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS) in cancer cells, as well as hypotheses on the molecular mechanisms that trigger this alteration. The role of hypoxia-inducible transcription factors, tumor suppressors, and the oncogenetic link between hypoxia-related enzymes, bioenergetic changes, and GI cancer are also discussed. This review emphasizes the potential of targeting bioenergetic regulators for anti-cancer therapy, particularly for GI cancers. Emphasizing the potential of targeting bioenergetic regulators for GI cancer therapy, the review categorizes these regulators into aerobic glycolysis/ lactate biosynthesis/transportation and TCA cycle/coupled OXPHOS. We also detail various anti-cancer drugs and strategies that have produced pre-clinical and/or clinical evidence in treating GI cancers, as well as the challenges posed by these drugs. Here we highlight that understanding dysregulated cancer cell bioenergetics is critical for effective treatments, although the diverse metabolic patterns present challenges for targeted therapies. Further research is needed to comprehend the specific mechanisms of inhibiting bioenergetic enzymes, address side effects, and leverage high-throughput multi-omics and spatial omics to gain insights into cancer cell heterogeneity for targeted bioenergetic therapies.
Core Tip: This review discusses the bioenergetic alteration and metabolic reprogramming in gastrointestinal (GI) cancers, including the interplay between aerobic glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. The review also highlights potential strategies for targeting bioenergetic regulators for anti-cancer therapy in GI cancers, summarizing the efficacy and challenges of several drugs.
