胃肠道间质瘤的下游存活通路：机制及意义
Downstream Survival Pathways in Gastrointestinal Stromal Tumors: Mechanisms and Significance
DOI: 10.12677/acm.2026.1641731, PDF,    科研立项经费支持
作者: 祁邓平, 韦党升, 韦春莹：右江民族医学院临床医学院，广西 百色；钟晓刚*：广西壮族自治区人民医院结直肠肛门外科，广西 南宁
关键词: 胃肠道间质瘤；下游存活通路；耐药；Gastrointestinal Stromal Tumor； Downstream Pro-Survival Pathways； Drug Resistance
摘要: 胃肠道间质瘤(gastrointestinal stromal tumor, GIST)是一类主要由KIT或PDGFRA激活性突变驱动的间叶性肿瘤。伊马替尼等酪氨酸激酶抑制剂(tyrosine kinase inhibitors, TKIs)显著改善了GIST的临床结局，但获得性耐药仍普遍存在。研究表明，GIST对伊马替尼的耐药并非单一由KIT突变所致，而是与下游存活信号通路的持续激活和重连密切相关。KIT/PDGFRA激活可启动PI3K-AKT-mTOR、RAS-RAF-MEK-ERK、JAK-STAT及SRC/FAK等多条信号通路，通过抑制凋亡、调控代谢重编程及诱导保护性自噬，共同维持肿瘤细胞在治疗压力下的存活。本文系统综述了GIST下游存活信号通路的组成及其在伊马替尼耐药形成中的作用，旨在为探索联合治疗策略及潜在生物标志物提供理论依据。
Abstract: Gastrointestinal stromal tumor (GIST) is a mesenchymal malignancy predominantly driven by activating mutations in KIT or PDGFRA. Tyrosine kinase inhibitors (TKIs), such as imatinib, have markedly improved clinical outcomes in GIST; however, acquired resistance remains common. Evidence indicates that resistance to imatinib is not solely attributable to KIT mutations but is closely associated with persistent activation and rewiring of downstream pro-survival signaling pathways. Activation of KIT/PDGFRA can initiate multiple signaling cascades, including PI3K-AKT-mTOR, RAS-RAF-MEK-ERK, JAK-STAT, and SRC/FAK, which collectively sustain tumor cell survival under therapeutic stress by inhibiting apoptosis, regulating metabolic reprogramming, and inducing cytoprotective autophagy. This review systematically summarizes the composition of downstream pro-survival signaling networks in GIST and their roles in the development of imatinib resistance, aiming to provide a theoretical basis for exploring combination therapeutic strategies and potential biomarkers.
文章引用：祁邓平, 钟晓刚, 韦党升, 韦春莹. 胃肠道间质瘤的下游存活通路：机制及意义[J]. 临床医学进展, 2026, 16(4): 4594-4599. https://doi.org/10.12677/acm.2026.1641731

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