Spitaleri Gianluca, Biffi Roberto, Barberis Massimo, Fumagalli Caterina, Toffalorio Francesca, Catania Chiara, Noberasco Cristina, Lazzari Chiara, de Marinis Filippo, De Pas Tommaso
Division of Chest Medical Oncology, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
Division of Abdominal Surgery, Rare Tumors and Sarcomas, European Institute of Oncology, Milan, Italy.
Onco Targets Ther. 2015 Aug 18;8:1997-2003. doi: 10.2147/OTT.S81558. eCollection 2015.
The development of gastrointestinal stromal tumors (GISTs) is largely driven by mutations in the KIT and PDGFRα genes. Imatinib mesylate is an oral small molecular tyrosine kinase inhibitor that mainly targets abl, c-KIT, and PDGFRα. Imatinib achieves disease control in approximately 70%-85% of patients with advanced GIST, and the median progression-free survival is 20-24 months. The efficacy of imatinib correlates with tumor kinase mutational status (exon 11 mutations mainly), and some mutations are known to be responsible for primary and secondary imatinib resistance. Beyond these, there are many other mutations that are considered rare and are associated with unknown clinical behavior. In the literature, there are poor and inconsistent data about the inhibitor sensitivity of mutations occurring in the activation-loop domain encoded by exon 17. In this article, we focus on a case of a patient suffering from GIST, harboring an extremely rare KIT activation-loop domain mutation (exon 17 mutation pN822K) treated with imatinib. A review of the literature is also presented.
胃肠道间质瘤（GISTs）的发展很大程度上由KIT和PDGFRα基因突变驱动。甲磺酸伊马替尼是一种口服小分子酪氨酸激酶抑制剂，主要靶向abl、c-KIT和PDGFRα。伊马替尼可使约70%-85%的晚期GIST患者病情得到控制，无进展生存期的中位数为20-24个月。伊马替尼的疗效与肿瘤激酶突变状态（主要是外显子11突变）相关，已知一些突变是原发性和继发性伊马替尼耐药的原因。除此之外，还有许多其他被认为罕见的突变，它们与未知的临床行为有关。在文献中，关于外显子17编码的激活环结构域中发生的突变的抑制剂敏感性的数据很少且不一致。在本文中，我们重点介绍了一例患有GIST的患者，该患者携带一种极其罕见的KIT激活环结构域突变（外显子17突变pN822K），接受了伊马替尼治疗。同时还对文献进行了综述。
