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World J Gastrointest Oncol. Jan 15, 2022; 14(1): 1-18
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.1
Molecular regulatory mechanism of ferroptosis and its role in gastrointestinal oncology: Progress and updates
Fan Yang, Si-Yu Sun, Sheng Wang, Jin-Tao Guo, Xiang Liu, Nan Ge, Guo-Xin Wang
Fan Yang, Si-Yu Sun, Sheng Wang, Jin-Tao Guo, Xiang Liu, Nan Ge, Guo-Xin Wang, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Author contributions: Yang F wrote the paper; Sun SY, Wang S, Guo JT, Liu X, Ge N, and Wang GX collected the data.
Supported by China Postdoctoral Science Foundation, No. 2020M670101ZX; Doctoral Scientific Research Foundation of Liaoning Province, No. 2019-BS-276; Science and Technology Program of Shenyang, No. 19-112-4-103; Youth Support Foundation of China Medical University, No. QGZ2018058; Scientific Fund of Shengjing Hospital, No. 201801; and 345 Talent Project of Shengjing Hospital, No. 52-30C.
Conflict-of-interest statement: The authors have no conflict of interests to declare 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: Si-Yu Sun, MD, PhD, Chief Doctor, Doctor, Professor, Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110004, Liaoning Province, China. sun-siyu@163.com
Received: April 20, 2021
Peer-review started: April 20, 2021
First decision: July 29, 2021
Revised: August 4, 2021
Accepted: December 7, 2021
Article in press: December 7, 2021
Published online: January 15, 2022
Abstract

Gastrointestinal (GI) tumors, including liver, pancreatic, gastric, and colorectal cancers, have a high incidence rate and low survival rate due to the lack of effective therapeutic methods and frequent relapses. Surgery and postoperative chemoradiotherapy have largely reduced the fatality rates for most GI tumors, but these therapeutic approaches result in poor prognoses due to severe adverse reactions and the development of drug resistance. Recent studies have shown that ferroptosis plays an important role in the onset and progression of GI tumors. Ferroptosis is a new non-apoptotic form of cell death, which is iron-dependent, non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species (ROS). The activation of ferroptosis can lead to tumor cell death. Thus, regulating ferroptosis in tumor cells may become a new therapeutic approach for tumors, making it become a research hotspot. Current studies suggest that ferroptosis is mainly triggered by the accumulation of lipid ROS. Furthermore, several studies have indicated that ferroptosis may be a new approach for the treatment of GI tumors. Here, we review current research progress on the mechanism of ferroptosis, current inducers and inhibitors of ferroptosis, and the role of ferroptosis in GI tumors to propose new methods for the treatment of such tumors.

Keywords: Ferroptosis, Gastrointestinal oncology, Hepatocellular carcinoma, Pancreatic cancer, Gastric cancer, Colorectal cancer

Core Tip: Ferroptosis refers to cell death triggered by iron-dependent lipid peroxidation. Recent studies have demonstrated that ferroptosis is involved in the onset and progression of numerous gastrointestinal (GI) tumors. Hence, inducing ferroptosis in tumor cells may become a new therapeutic strategy against GI tumors. Here, we review the molecular mechanism of ferroptosis and its role in GI tumors, with the aim of providing new research directions and ideas for the treatment of GI tumors.