Joensuu Heikki, Fletcher Christopher, Dimitrijevic Sasa, Silberman Sandra, Roberts Peter, Demetri George
Department of Oncology and Radiotherapy, Helsinki University Central Hospital, Helsinki, Finland.
Lancet Oncol. 2002 Nov;3(11):655-64. doi: 10.1016/s1470-2045(02)00899-9.
Gastrointestinal stromal tumours (GISTs) are the most common form of mesenchymal tumour of the gastrointestinal tract. Clinically, they range from small indolent tumours curable with surgery alone to aggressive cancers. Making a distinction between an indolent and a malignant GIST is unreliable with conventional histopathological techniques. The presence of metastases at the time of diagnosis confirms malignancy, but all GISTs should be regarded as having malignant potential. GISTs characteristically express the KIT protein, a transmembrane tyrosine kinase receptor for stem-cell factor. Most GISTs have a mutation in the KIT proto-oncogene that translates into a gain-of-function constitutive activation of the KIT kinase. KIT activation seems to be an early tumour-promoting event in pathogenesis. Commonly, malignant GISTs show high-level primary resistance to conventional chemotherapy. Imatinib mesylate is an orally administered selective inhibitor of certain tyrosine kinases including KIT. Most patients with advanced malignant GISTs achieve clinical benefit and significant antitumour responses with imatinib mesylate. Responses have been durable, and most patients tolerate the drug well at clinically effective doses. Imatinib mesylate is the first effective systemic therapy for advanced GIST.
胃肠道间质瘤（GISTs）是胃肠道间充质肿瘤最常见的形式。临床上，它们范围从仅通过手术即可治愈的小的惰性肿瘤到侵袭性癌症。用传统的组织病理学技术区分惰性和恶性GIST是不可靠的。诊断时出现转移可确诊为恶性，但所有GIST都应被视为具有恶性潜能。GISTs特征性地表达KIT蛋白，一种干细胞因子的跨膜酪氨酸激酶受体。大多数GIST在KIT原癌基因中有一个突变，该突变转化为KIT激酶的功能获得性组成性激活。KIT激活似乎是发病机制中早期的肿瘤促进事件。通常，恶性GIST对传统化疗表现出高度的原发性耐药。甲磺酸伊马替尼是一种口服的某些酪氨酸激酶（包括KIT）的选择性抑制剂。大多数晚期恶性GIST患者使用甲磺酸伊马替尼可获得临床益处和显著的抗肿瘤反应。反应持久，大多数患者在临床有效剂量下对该药物耐受性良好。甲磺酸伊马替尼是晚期GIST的首个有效全身治疗药物。
