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World J Gastrointest Pathophysiol. Sep 22, 2025; 16(3): 107834
Published online Sep 22, 2025. doi: 10.4291/wjgp.v16.i3.107834
CRISPR/Cas9 gene editing in gastric cancer: Mechanisms, advances, and therapeutic potential
Grigorios Christodoulidis, Dimitra Bartzi, Kyriaki Tsagkidou, Alexandra Dimaki, Lydia Lazaridou, Kalliopi Vakalou, Konstantinos E Koumarelas, Dimitrios Schizas
Grigorios Christodoulidis, Alexandra Dimaki, Lydia Lazaridou, Kalliopi Vakalou, Department of General Surgery, University Hospital of Larissa, Larissa 41110, Thessalia, Greece
Dimitra Bartzi, Department of Oncology, The 251 Airforce General Hospital, Athens 11525, Greece
Kyriaki Tsagkidou, Department of Gastroenterology, University Hospital of Larisa, Larisa 41100, Thessalia, Greece
Konstantinos E Koumarelas, Department of General and Orthopaedic Surgery, Luzerner Kantonsspital Wolhusen, Luzern 6110, Switzerland
Dimitrios Schizas, Department of First Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
Co-first authors: Grigorios Christodoulidis and Dimitra Bartzi.
Author contributions: Christodoulidis G designed the overall concept and outline of the manuscript; Christodoulidis G and Bartzi D contributed equally to this article and are the co-first authors of this manuscript; Christodoulidis G, Bartzi D, Tsagkidou K, Dimaki A, Lazaridou L, Vakalou K, Koumarelas KE, and Schizas D contributed to the discussion and design of the manuscript, contributed to the writing, editing the manuscript, and literature review; all authors thoroughly reviewed and endorsed the final manuscript.
Conflict-of-interest statement: The authors report no relevant conflicts of interest 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: Grigorios Christodoulidis, MD, PhD, Department of General Surgery, University Hospital of Larissa, Mezourlo, Larissa 41110, Thessalia, Greece. gregsurg@yahoo.gr
Received: March 31, 2025
Revised: April 22, 2025
Accepted: June 16, 2025
Published online: September 22, 2025
Processing time: 174 Days and 14.2 Hours
Abstract

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, necessitating innovative approaches for its diagnosis and treatment. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), a revolutionary gene-editing technology, has emerged as a powerful tool for unraveling the molecular mechanisms underlying GC and for advancing precision medicine strategies. This review explores the current applications of CRISPR/Cas9 in GC research, including the identification of oncogenes and tumor suppressors, modeling tumor microenvironment interactions, and developing gene-based therapies. We highlight recent breakthroughs in genome editing that have enhanced our understanding of GC pathogenesis and resistance mechanisms to conventional therapies. Additionally, we discuss the potential of CRISPR/Cas9 for therapeutic gene editing in GC, addressing challenges such as off-target effects, delivery methods, and ethical considerations. By summarizing the progress and limitations of CRISPR/Cas9 in GC, this review aims to provide a comprehensive perspective on how this transformative technology could shape future strategies for the prevention, diagnosis, and treatment of GC.

Keywords: Gastric cancer; Gene-editing technologies; Clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9; Helicobacter pylori; Precision genome editing

Core Tip: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing has emerged as a transformative tool in gastric cancer research, offering precise manipulation of oncogenes and tumor suppressor genes. This technology facilitates the dissection of gastric tumorigenesis mechanisms and the development of targeted therapies. Recent advances highlight its potential in overcoming chemotherapy resistance and enhancing immunotherapeutic strategies. Despite challenges such as off-target effects and delivery mechanisms, ongoing research continues to refine CRISPR/Cas9 applications, underscoring its promise in improving outcomes for gastric cancer patients.