Wang J, Pei Q, Yu NH. Anti-EGFR treatment resistance in patients with wild-type RAS metastatic colorectal cancer: Three case reports. World J Gastrointest Oncol 2026; 18(3): 114379 [DOI: 10.4251/wjgo.v18.i3.114379]
Corresponding Author of This Article
Nan-Hui Yu, PhD, Associate Professor, Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. yunanhui@csu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Report
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/
Mar 15, 2026 (publication date) through Mar 12, 2026
Times Cited of This Article
Times Cited (0)
Journal Information of This Article
Publication Name
World Journal of Gastrointestinal Oncology
ISSN
1948-5204
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Wang J, Pei Q, Yu NH. Anti-EGFR treatment resistance in patients with wild-type RAS metastatic colorectal cancer: Three case reports. World J Gastrointest Oncol 2026; 18(3): 114379 [DOI: 10.4251/wjgo.v18.i3.114379]
World J Gastrointest Oncol. Mar 15, 2026; 18(3): 114379 Published online Mar 15, 2026. doi: 10.4251/wjgo.v18.i3.114379
Anti-EGFR treatment resistance in patients with wild-type RAS metastatic colorectal cancer: Three case reports
Jing Wang, Qian Pei, Nan-Hui Yu
Jing Wang, Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Qian Pei, Department of Gastrointestinal Surgery, The Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Nan-Hui Yu, Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Co-first authors: Jing Wang and Qian Pei.
Author contributions: Wang J and Pei Q contributed to manuscript writing, data collection. and data analysis; Yu NH contributed to study design and manuscript editing. All authors have read and approve the final manuscript. Wang J and Pei Q contributed equally to this work.
Supported by the Natural Science Foundation of Hunan Province (2023JJ40977).
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: This article does not involve any conflict of competing interest.
CARE Checklist (2016) statement: The authors have read CARE Checklist (2016), and the manuscript was prepared and revised according to CARE Checklist (2016).
Corresponding author: Nan-Hui Yu, PhD, Associate Professor, Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. yunanhui@csu.edu.cn
Received: September 18, 2025 Revised: October 24, 2025 Accepted: January 22, 2026 Published online: March 15, 2026 Processing time: 175 Days and 20.3 Hours
Abstract
BACKGROUND
Anti-EGFR therapy markedly improves outcomes in advanced colorectal cancer (CRC) patients. Nonetheless, resistance to this treatment is commonly observed even in patients with wild-type RAS tumors.
CASE SUMMARY
In this study, three patients with wild-type RAS metastatic CRC with anti-EGFR resistance were comprehensively assessed for genetic alterations (KRAS, NRAS, BRAF, and PIK3CA mutations; HER2 expression) in primary and metastatic lesions. Among the subjects, two exhibited acquired resistance to anti-EGFR therapy following an initial treatment response. One of these patients developed a KRAS mutation in metastatic lesions, while the other had HER2 overexpression in the primary tumor. The third patient demonstrated primary resistance, attributed to a preexisting KRAS mutation in a metastatic lesion that was not present in the primary tumor.
CONCLUSION
These cases underscore a critical need to understand the diverse mechanisms of resistance to anti-EGFR treatment in patients with wild-type RAS metastatic CRC. Despite the limited sample size, comprehensive genetic profiling of both primary and, when feasible, metastatic lesions is recommended prior to therapy initiation. Furthermore, HER2-targeted therapy could be beneficial for patients with HER2 amplification/overexpression. A multidisciplinary approach and ongoing molecular monitoring remain vital in the management of advanced CRC.
Core Tip: In this study, 3 wild-type RAS metastatic colorectal cancer patients with anti-EGFR resistance were analyzed. Key findings: Acquired resistance is associated with KRAS mutation/HER-2 amplification and primary resistance is associated with metastatic KRAS mutation (tumor heterogeneity). These findings suggest essential genetic profiling of primary/metastatic lesions (pyrosequencing for KRAS/NRAS/BRAF/PIK3CA and IHC+FISH for HER-2) and HER-2-targeted therapy for overexpression.
