Wang C, Zhang J, Chen ZK, Wang YG, Shi M. Advances and challenges of chimeric antigen receptor T cell therapy in digestive system malignancies. World J Clin Oncol 2026; 17(2): 114107 [DOI: 10.5306/wjco.v17.i2.114107]
Corresponding Author of This Article
Min Shi, MD, Chief Physician, Professor, Department of Gastroenterology, Shanghai Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Changning District, Shanghai 200336, China. sm1790@shtrhospital.com
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Oncology
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Minireviews
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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/
Feb 24, 2026 (publication date) through Feb 12, 2026
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Publication Name
World Journal of Clinical Oncology
ISSN
2218-4333
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Wang C, Zhang J, Chen ZK, Wang YG, Shi M. Advances and challenges of chimeric antigen receptor T cell therapy in digestive system malignancies. World J Clin Oncol 2026; 17(2): 114107 [DOI: 10.5306/wjco.v17.i2.114107]
World J Clin Oncol. Feb 24, 2026; 17(2): 114107 Published online Feb 24, 2026. doi: 10.5306/wjco.v17.i2.114107
Advances and challenges of chimeric antigen receptor T cell therapy in digestive system malignancies
Chen Wang, Jin Zhang, Zi-Ke Chen, Yu-Gang Wang, Min Shi
Chen Wang, Zi-Ke Chen, Yu-Gang Wang, Min Shi, Department of Gastroenterology, Shanghai Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Jin Zhang, Department of Traditional Medicine, Kongjiang Community Health Service Center, Shanghai 200082, China
Co-first authors: Chen Wang and Jin Zhang.
Co-corresponding authors: Yu-Gang Wang and Min Shi.
Author contributions: Wang C and Zhang J were the primary contributors to the manuscript writing and they contributed equally to this manuscript as co-first authors; Chen ZK revised the manuscript; Wang YG and Shi M conceptualized the theme and structure of this manuscript and they contributed equally to this manuscript as co-corresponding authors. All authors have read and approved the final manuscript.
Supported by Pujiang Project of Shanghai Magnolia Talent Plan, No. 24PJD098; Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality, No. 23ZR1458300; and Key Discipline Project of Shanghai Municipal Health System, No. 2024ZDXK0004.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Min Shi, MD, Chief Physician, Professor, Department of Gastroenterology, Shanghai Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Changning District, Shanghai 200336, China. sm1790@shtrhospital.com
Received: September 11, 2025 Revised: October 23, 2025 Accepted: December 25, 2025 Published online: February 24, 2026 Processing time: 147 Days and 23.4 Hours
Abstract
Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized the treatment of hematologic malignancies, but its success in solid tumors, particularly those of the digestive system, remains limited. Tumors of the gastrointestinal system, including gastric, colorectal, esophageal, hepatic, and pancreatic malignancies, represent a significant global health burden with high morbidity and mortality. Recent advances in antigen selection, chimeric antigen receptor design, delivery techniques, and combinatorial approaches have sparked renewed interest in CAR-T immunotherapy for these cancers. This article discusses recent progress in CAR-T development across the major digestive system tumors, outlines tumor-specific targets and clinical trials, highlights prevailing challenges and potential solutions, and proposes strategic directions for the next generation of CAR-T therapies in solid tumors.
Core Tip: Chimeric antigen receptor T cell therapy (CAR) has achieved remarkable success in hematologic cancers but faces unique barriers in solid tumors of the digestive system. This article highlights recent progress in optimizing antigen selection, CAR engineering, and delivery strategies, while discussing tumor-specific targets and clinical trials in gastric, colorectal, esophageal, hepatic, and pancreatic cancers. By addressing challenges such as the tumor microenvironment and therapeutic resistance, we provide perspectives on advancing CAR T cell therapy immunotherapy toward safe, effective, and durable treatments for gastrointestinal malignancies.
