Jiang YK, Li W, Qiu YY, Yue M. Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer. World J Gastrointest Oncol 2024; 16(6): 2318-2334 [PMID: 38994153 DOI: 10.4251/wjgo.v16.i6.2318]
Corresponding Author of This Article
Meng Yue, MM, Doctor, Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, No. 105 Jiefang Road, Jinan 250013, Shandong Province, China. mengtiger78@163.com
Research Domain of This Article
Medicine, Research & Experimental
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 Gastrointest Oncol. Jun 15, 2024; 16(6): 2318-2334 Published online Jun 15, 2024. doi: 10.4251/wjgo.v16.i6.2318
Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer
Ya-Kun Jiang, Wei Li, Ying-Yang Qiu, Meng Yue
Ya-Kun Jiang, Meng Yue, Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
Wei Li, Health Management Center, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
Ying-Yang Qiu, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
Author contributions: Jiang YK wrote the manuscript; Li W and Qiu YY collected the data; Yue M guided the manuscript; all authors reviewed, edited, and approved the final manuscript and revised it critically for important intellectual content, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.
Conflict-of-interest statement: All the authors declare no conflict of interest.
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: Meng Yue, MM, Doctor, Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, No. 105 Jiefang Road, Jinan 250013, Shandong Province, China. mengtiger78@163.com
Received: December 11, 2023 Revised: April 4, 2024 Accepted: April 18, 2024 Published online: June 15, 2024 Processing time: 186 Days and 19.7 Hours
Abstract
Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.
Core Tip: Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and magtuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.
