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REVIEW article

Front. Oncol.

Sec. Molecular and Cellular Oncology

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1581920

The effect of ubiquitination and deubiquitination to imatinib resistance in gastrointestinal stromal tumors

Provisionally accepted
  • 1Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University,, Xi'an, China
  • 2State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China

The final, formatted version of the article will be published soon.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor. Imatinib, as a receptor-type tyrosine kinase inhibitor (TKI), becomes a first-line drug for adjuvant therapy and prognosis. However, patients are facing with the problem of primary and secondary drug resistance when using imatinib, which affects the effect of imatinib. Thus, it is particularly important to explore the mechanism of drug resistance. Ubiquitination and deubiquitination process have been proofed to performance as posttranslational modifications (PTMs) to influence the occurrence and progression of most tumors. Hence, we attach importance to these mechanisms and found that GIST resistance may be related to ubiquitination and deubiquitination in regulating exosome secretion, autophagy, apoptosis and ferroptosis. Through clarifying these connections, this review aims to offers insights and hope for therapeutic advancements of imatinib-resistant GIST patients and the use of specific ubiquitin modifications as markers in the future.

Keywords: Gastrointestinal Stromal Tumors, Imatinib, Drug Resistance, Ubiquitination modifications, Deubiquitination modification

Received: 23 Feb 2025; Accepted: 02 Jul 2025.

Copyright: © 2025 Huo, Li, Wang, Zhao and Yang. 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: Jianjun Yang, Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University,, Xi'an, China

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