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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1648-1667
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1648
Regulatory role of the transforming growth factor-β signaling pathway in the drug resistance of gastrointestinal cancers
Xiaoqun Lv, Guoxiong Xu
Xiaoqun Lv, Department of Pharmacy, Jinshan Hospital, Fudan University, Shanghai 201508, China
Guoxiong Xu, Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, China
Guoxiong Xu, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Author contributions: Lv XQ contributed to the acquisition and analysis of data and writing the paper; Xu G contributed to the design of the study and writing the paper.
Supported by Fourth Training Program for the Outstanding Young Talents, Jinshan Health Commission, China, No. JSYQ201904; Key Construction Project on Clinical Pharmacy of Shanghai, China, No. 2019-1229; and National Natural Science Foundation of China, No. 81872121.
Conflict-of-interest statement: The authors declare that they have no conflicting 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 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/
Corresponding author: Guoxiong Xu, MD, PhD, Academic Fellow, Director, Full Professor, Senior Scientist, Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai 201508, China. guoxiong.xu@fudan.edu.cn
Received: April 29, 2021
Peer-review started: April 29, 2021
First decision: June 16, 2021
Revised: June 28, 2021
Accepted: August 18, 2021
Article in press: August 18, 2021
Published online: November 15, 2021
Abstract

Gastrointestinal (GI) cancer, including esophageal, gastric, and colorectal cancer, is one of the most prevalent types of malignant carcinoma and the leading cause of cancer-related deaths. Despite significant advances in therapeutic strategies for GI cancers in recent decades, drug resistance with various mechanisms remains the prevailing cause of therapy failure in GI cancers. Accumulating evidence has demonstrated that the transforming growth factor (TGF)-β signaling pathway has crucial, complex roles in many cellular functions related to drug resistance. This review summarizes current knowledge regarding the role of the TGF-β signaling pathway in the resistance of GI cancers to conventional chemotherapy, targeted therapy, immunotherapy, and traditional medicine. Various processes, including epithelial-mesenchymal transition, cancer stem cell development, tumor microenvironment alteration, and microRNA biogenesis, are proposed as the main mechanisms of TGF-β-mediated drug resistance in GI cancers. Several studies have already indicated the benefit of combining antitumor drugs with agents that suppress the TGF-β signaling pathway, but this approach needs to be verified in additional clinical studies. Moreover, the identification of potential biological markers that can be used to predict the response to TGF-β signaling pathway inhibitors during anticancer treatments will have important clinical implications in the future.

Keywords: Drug resistance, Gastrointestinal cancer, Transforming growth factor-β, Epithelial-mesenchymal transition, Cancer stem cells, MicroRNAs

Core Tip: The transforming growth factor (TGF)-β signaling pathway is involved in the drug resistance of gastrointestinal (GI) cancers. This review summarizes the current understanding of the roles played by the TGF-β signaling pathway in resistance to conventional chemotherapy, targeted therapy, immunotherapy, and traditional medicine in GI cancers as well as the various processes by which this occurs, including epithelial-mesenchymal transition, cancer stem cell development, tumor microenvironment alteration, and microRNA biogenesis.