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Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2023; 29(6): 926-948
Published online Feb 14, 2023. doi: 10.3748/wjg.v29.i6.926
Resistance to targeted therapy in metastatic colorectal cancer: Current status and new developments
Yuan-Ling Tang, Dan-Dan Li, Jia-Yu Duan, Lei-Ming Sheng, Xin Wang
Yuan-Ling Tang, Dan-Dan Li, Jia-Yu Duan, Lei-Ming Sheng, Xin Wang, Department of Radiation Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Yuan-Ling Tang, Dan-Dan Li, Jia-Yu Duan, Lei-Ming Sheng, Xin Wang, Department of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Wang X designed the research study; Tang YL performed the research and wrote the manuscript; Li DD contributed new reagents; Duan JY revised this review; Sheng LM summarized the citation and wrote the table; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82073338; Sichuan Science and Technology Support Project, No. 2021YFSY0039 and No. 22ZDYF0499; 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University, No. 2020HXFH002; 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University, No. ZYJC21059.
Conflict-of-interest statement: There are no conflicts of interest to report.
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: Xin Wang, MD, PhD, Doctor, Department of Radiation Oncology, Cancer Center, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu 610041, Sichuan Province, China. 2079248480@qq.com
Received: September 20, 2022
Peer-review started: September 20, 2022
First decision: December 12, 2022
Revised: December 24, 2022
Accepted: January 30, 2023
Article in press: January 30, 2023
Published online: February 14, 2023
Processing time: 142 Days and 9.5 Hours
Abstract

Colorectal cancer (CRC) is one of the most lethal and common malignancies in the world. Chemotherapy has been the conventional treatment for metastatic CRC (mCRC) patients. However, the effects of chemotherapy have been unsatisfactory. With the advent of targeted therapy, the survival of patients with CRC have been prolonged. Over the past 20 years, targeted therapy for CRC has achieved substantial progress. However, targeted therapy has the same challenge of drug resistance as chemotherapy. Consequently, exploring the resistance mechanism and finding strategies to address the resistance to targeted therapy, along with searching for novel effective regimens, is a constant challenge in the mCRC treatment, and it is also a hot research topic. In this review, we focus on the current status on resistance to existing targeted therapies in mCRC and discuss future developments.

Keywords: Colorectal cancer; Targeted treatment; Resistance; New development

Core Tip: Colorectal cancer (CRC) is one of the most lethal and common malignancies in the world. Chemotherapy has long been the mainstay of CRC treatment. However, since chemotherapy is not a specific regimen, it will produce systemic toxicity. Following, with the advent of targeted therapy, the prognosis of CRC has been improved significantly. Although targeted therapy also develop drug resistance, more and more novel targets and combination regimens are being explored over the past 20 years. In this review, we summarized resistance to exiting targeted therapy, and discussed future developments in CRC.