Imatinib mesylate: past successes and future challenges in the treatment of gastrointestinal stromal tumors.
Imatinib mesylate: past successes and future challenges in the treatment of gastrointestinal stromal tumors.
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DOI：
10.4137/cmo.s4259
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Ksienski D
中科院分区：
文献类型：
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作者：
Ksienski D
就在十多年前，胃肠道肿瘤是一种知之甚少的间叶肿瘤，无法用化疗成功治疗。晚期疾病的细胞毒性治疗产生的反应率为10%，中位生存期仅为18个月。然而，KIT和血小板衍生生长因子受体α（PDGFRA）突变作为大多数胃肠道肿瘤的致癌驱动因素的发现，为靶向治疗铺平了道路。甲磺酸伊马替尼是一种酪氨酸激酶抑制剂，在转移性疾病中的临床获益率（完全缓解、部分缓解和疾病稳定）超过80%，中位生存期为57个月。伊马替尼现在也被批准用于KIT阳性GIST切除术后的成人患者。对伊马替尼的作用机制、独特的药代动力学、耐药性和低度但慢性不良反应的管理的主要见解仍在继续。
Just over a decade ago, gastrointestinal tumours were a poorly understood mesenchymal neoplasm unsuccessfully treated with chemotherapy. Cytotoxic therapy for advanced disease yielded response rates of 10% and median survival of just 18 months. However, the discovery of KIT and platelet derived growth factor receptor alpha (PDGFRA) mutations as oncogenic drivers of most gastrointestinal tumours, paved the way for targeted therapy. Imatinib mesylate, a tyrosine kinase inhibitor, produces a clinical benefit rate (complete response, partial response, and stable disease) of more than 80% in metastatic setting and a median survival of 57 months. Imatinib is now also approved in adult patients following resection of KIT-positive GIST. Major insights into the mechanism of action of imatinib, unique pharmacokinetics, drug resistance, and management of low grade but chronic adverse effects continue to be made.