REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1628729
Therapeutic Potential of TRIM Family Proteins in Gastric Cancer: From Signaling Pathway Regulation to Precision Targeting Strategies
Provisionally accepted
- 1Nanchang University, Jiangxi Medical College, the third Clinical Medical College (The First Hospital of Nanchang), Nanchang, China
- 2Nanchang University, Jiangxi Medical College, the 1st affiliated hospital, Nanchang, China
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Gastric cancer (GC) is a globally prevalent malignant tumor, causing approximately 770,000 deaths in 2020, ranking fourth among all cancers. The tripartite motif (TRIM) protein family is involved in various cellular regulations and has become a key player in the pathogenesis of gastric cancer. This review explores the therapeutic potential of TRIM proteins in gastric cancer, from signaling pathway regulation to precision targeting strategies. Structurally, there are differences in the C-terminal domain of TRIM proteins, which determine their subgroup classification and substrate recognition. Functionally, they regulate multiple signaling pathways that are crucial for the development of gastric cancer. Clinically, many TRIM proteins serve as promising diagnostic and prognostic biomarkers. In terms of therapy, targeting TRIM proteins holds great potential. Strategies include developing small molecule inhibitors targeting specific TRIM domains, such as inhibitors targeting the bromodomain of TRIM24, and exploring PROTAC technology to degrade oncogenic TRIM proteins. Combination immunotherapy targeting TRIM-related pathways may also provide new therapeutic options. However, challenges persist, Including limited understanding of heterotypic polyubiquitination targets/functions of TRIM proteins, insufficient mechanistic/epidemiological insights into their immunomodulatory roles in the tumor microenvironment, underdeveloped TRIM inhibitors for gastric cancer, unevaluated pharmacokinetics/toxicity of inhibitors in preclinical models, and the need to construct complete TRIM biological systems. In summary, TRIM proteins are deeply involved in the biological processes of gastric cancer, and understanding their functions and regulation could lead to the development of more effective precision targeting strategies for gastric cancer treatment.
Keywords: ：TRIM Proteins, gastric cancer, oncogenesis, Targeting strategies, Mechanism
Received: 14 May 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Zhao, Qi, Zhang, Feng, Fang and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ziling Fang, Nanchang University, Jiangxi Medical College, the 1st affiliated hospital, Nanchang, China
Nian Fang, Nanchang University, Jiangxi Medical College, the third Clinical Medical College (The First Hospital of Nanchang), Nanchang, China
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