World J Gastrointest Oncol. Dec 15, 2026; 18(12): 123408 Published online Dec 15, 2026. doi: 10.4251/wjgo.123408
Tumor-treating fields in gastrointestinal cancers: Mechanisms, clinical evidence, and emerging precision therapy
Chern E Oon, Bilgin Keserci
Chern E Oon, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang 11800, Malaysia
Bilgin Keserci, Research and Development Center, JRX Global Sdn. Bhd., Petaling Jaya 47301, Selangor, Malaysia
Author contributions: Oon CE conceptualized the article, performed the literature review, drafted the manuscript, and designed the conceptual framework and figure; Keserci B contributed to the biophysical interpretation of field delivery and critically revised the manuscript for technical accuracy; all authors approved the final version.
AI contribution statement: During manuscript preparation, the authors used ChatGPT and Quillbot solely for language polishing, grammar correction, and structural refinement due to limited access to professional human language editors. The authors independently authored, reviewed, and verified all scientific content, data analysis, interpretation, and references. No AI tools were used to generate or modify any scientific content, and the authors take full responsibility for the accuracy and integrity of the final manuscript.
Supported by JRX Global Sdn. Bhd, No. R504-LR-GAL007-0000002762-J157.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
Corresponding author: Chern E Oon, Associate Professor, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia. chern.oon@usm.my
Received: May 21, 2026 Revised: July 8, 2026 Accepted: August 5, 2026 Published online: December 15, 2026 Processing time: 176 Days and 2 Hours
Abstract
Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that convert physical energy into biological stress within dividing cancer cells. Initially recognized for their ability to disrupt mitosis, TTFields are now understood to influence a broader range of cancer-related processes, including DNA replication, repair pathways, cellular organization, and immunogenic cell death. These mechanisms are particularly relevant to gastrointestinal malignancies, where deep anatomy, stromal barriers, organ motion, peritoneal dissemination, and cumulative systemic toxicity limit conventional treatment escalation. Pancreatic cancer is currently the leading gastrointestinal indication for TTFields. In the PANOVA-3 trial, TTFields combined with standard chemotherapy improved overall survival without additional systemic toxicity, although tumor shrinkage and conventional progression-free survival remained unchanged. Evidence in hepatocellular, gastric, biliary tract, and colorectal cancers remains preliminary and should be interpreted as mechanistic or hypothesis-generating rather than practice-changing. This article argues that TTFields should not be understood as a simple on-or-off device exposure. In gastrointestinal oncology, their biological effect depends on the delivered intratumoral field intensity, tumor geometry, tissue conductivity, anatomical motion, biological susceptibility, treatment combination, and cumulative adherence. Therefore, we propose a precision field-delivery framework in which TTFields are planned, monitored, and adapted using patient-specific anatomy, tumor biology, exposure metrics, and clinically meaningful endpoints beyond radiographic shrinkage.
Core Tip: Tumor-treating fields are emerging as novel therapeutic platforms in gastrointestinal oncology, linking electric-field physics with tumor biology and patient-specific anatomy. This review highlights pancreatic cancer as the first clinically validated gastrointestinal proof point while critically examining earlier evidence in hepatocellular, gastric, biliary, and colorectal cancers. We propose that tumor-treating fields should be viewed not simply as uniform device exposure but as a patient-specific biophysical prescription. Future progress will depend on integrating computational field modeling, biological susceptibility, real-world treatment adherence, and adaptive planning to optimize effective intratumoral field exposure over time.
