Reichardt P, Pink D, Mrozek A, Lindner T, Hohenberger P
Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie.
Z Gastroenterol. 2004 Apr;42(4):327-31. doi: 10.1055/s-2004-812691.
The vast majority of mesenchymal tumors originating from the GI tract consists of gastrointestinal stromal tumors (GIST), an entity just recently defined. The incidence is estimated to be around 10 - 20/1000000, the median age at diagnosis has been reported to be 55 to 65 years. GISTs most commonly occur in the stomach or duodenum, followed by the small intestine. About half of the patients present with metastatic disease at first diagnosis, predominantly in the liver or periteneum. GISTs are strongly and uniformly positive for CD117 (c-kit), a type III receptor-tyrosine kinase. Kit mutations, mostly in exon 11, leading to ligand independent constitutive activation are supposed to play a major role in the pathogenesis of GIST. Until recently no active systemic treatment was available for advanced gastrointestinal stromal tumors. Imatinib (STI571 = Glivec) is a rationally designed, orally available phenylaminopyrimidin analogue. The mechanism of action consists of a competitive interaction with the ATP-binding pocket of specific tyrosine kinases. Early results from clinical trials with response rates around 60 % and progression arrest in more than 80 % of patients resulting in fast relief of symptoms, confirm the high activity of this novel treatment. The role of adjuvant treatment after potentially curative resection of GIST is currently evaluated in ongoing clinical trials. Patients with progressive disease while under treatment with Imatinib should be enrolled in studies testing novel treatment strategies as RAD001, PKC412 or SU11 248.
绝大多数起源于胃肠道的间充质肿瘤是胃肠道间质瘤（GIST），这是一种最近才被定义的实体瘤。据估计，其发病率约为10-20/1000000，据报道诊断时的中位年龄为55至65岁。GIST最常发生于胃或十二指肠，其次是小肠。约一半的患者在初次诊断时即出现转移性疾病，主要转移至肝脏或腹膜。GIST对CD117（c-kit）呈强阳性且一致阳性，CD117是一种III型受体酪氨酸激酶。Kit突变主要发生在外显子11，导致配体非依赖性组成性激活，被认为在GIST的发病机制中起主要作用。直到最近，晚期胃肠道间质瘤还没有有效的全身治疗方法。伊马替尼（STI571 = 格列卫）是一种经过合理设计的口服可用苯氨基嘧啶类似物。其作用机制包括与特定酪氨酸激酶的ATP结合口袋进行竞争性相互作用。临床试验的早期结果显示，缓解率约为60%，超过80%的患者病情进展停止，症状迅速缓解，证实了这种新疗法的高活性。目前正在进行的临床试验评估了GIST潜在治愈性切除术后辅助治疗的作用。在接受伊马替尼治疗期间病情进展的患者应参加测试新治疗策略的研究，如RAD001、PKC412或SU11 248。
