Ding Haixiang, Yu Xiuchong, Yu Yu, Lao Xifeng, Hang Chen, Gao Kaijun, Jia Yangtao, Yan Zhilong
Medical School of Ningbo University, Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Ningbo, Zhejiang 315211, P.R. China.
Department of Gastrointestinal Surgery, The Ningbo First Hospital and The Affiliated Hospital of The Medical School of Ningbo University, Ningbo, Zhejiang 315010, P.R. China.
Oncol Rep. 2020 Mar;43(3):751-764. doi: 10.3892/or.2020.7470. Epub 2020 Jan 17.
Gastrointestinal stromal tumors (GISTs) are the most commonly observed mesenchymal tumors of the digestive tract, and they originate from the interstitial cells of Cajal. GISTs can be divided into KIT/PDGFRA‑mutant GISTs and wild‑type GISTs based on the presence or absence of KIT/PDGFRA mutations. Wild‑type GISTs can be divided into succinate dehydrogenase complex (SDH)‑deficient GISTs and non‑SDH‑deficient GISTs. Downstream signaling pathways activated by these mutations serve a pivotal role in the development of GISTs and are associated with the biological behavior, including risk stratification, clinical prognosis and drug resistance. Accurate medical care requires accurate molecular diagnosis, which in turn prolongs the survival of patients with GISTs and makes GIST a chronic disease. At present, there is a lack of effective treatment for imatinib/sunitinib/regorafenib resistant patients and KIT/PDGFRA‑WT GISTs, which is undoubtedly a major challenge for future research. The present review summarizes the molecular pathogenesis of GISTs and the progress of related research.
胃肠道间质瘤(GISTs)是消化道最常见的间叶性肿瘤,起源于 Cajal 间质细胞。根据 KIT/PDGFRA 突变的有无,GISTs 可分为 KIT/PDGFRA 突变型 GISTs 和野生型 GISTs。野生型 GISTs 可分为琥珀酸脱氢酶复合物(SDH)缺陷型 GISTs 和非 SDH 缺陷型 GISTs。这些突变激活的下游信号通路在 GISTs 的发生发展中起关键作用,并与包括风险分层、临床预后和耐药性在内的生物学行为相关。准确的医疗需要准确的分子诊断,这反过来又延长了 GISTs 患者的生存期,并使 GIST 成为一种慢性病。目前,对于伊马替尼/舒尼替尼/瑞戈非尼耐药患者和 KIT/PDGFRA-WT GISTs 缺乏有效的治疗方法,这无疑是未来研究的一大挑战。本综述总结了 GISTs 的分子发病机制及相关研究进展。