Huo Huade, Li Haolin, Yang Xinlin, Wang Shu, Zhao Yan, Yang Jianjun
Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
State 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.
Front Oncol. 2025 Jul 25;15:1581920. doi: 10.3389/fonc.2025.1581920. eCollection 2025.
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.
胃肠道间质瘤（GIST）是最常见的间叶组织肿瘤。伊马替尼作为一种受体型酪氨酸激酶抑制剂（TKI），成为辅助治疗和预后的一线药物。然而，患者在使用伊马替尼时面临原发性和继发性耐药问题，这影响了伊马替尼的疗效。因此，探索耐药机制尤为重要。泛素化和去泛素化过程已被证明作为翻译后修饰（PTM）影响大多数肿瘤的发生和发展。因此，我们重视这些机制，发现GIST耐药可能与泛素化和去泛素化调节外泌体分泌、自噬、凋亡和铁死亡有关。通过阐明这些联系，本综述旨在为伊马替尼耐药GIST患者的治疗进展以及未来使用特定泛素修饰作为标志物提供见解和希望。
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