Ripretinib for the treatment of advanced, imatinib-resistant gastrointestinal stromal tumors

IF 2.3 3区 医学 Q3 GASTROENTEROLOGY & HEPATOLOGY Journal of Digestive Diseases Pub Date : 2023-09-14 DOI:10.1111/1751-2980.13229
Wei Zhen Liu, Yu Qiang Du, Qian Shen, Kai Xiong Tao, Peng Zhang
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Abstract

Discovery of constitutive activation of KIT/PDGFRA tyrosine kinases in gastrointestinal stromal tumors (GISTs) leads to the development of the targeted drug imatinib. However, the inevitable development of imatinib resistance remains a major issue. Ripretinib is a novel targeted drug that inhibits the activities of a broad spectrum of drug-resistant KIT/PDGFRA mutants. It was approved in 2020 and is currently recommended by major international guidelines as the fourth-line and beyond therapy for advanced GISTs. Emerging evidence shows that ripretinib is superior to sunitinib as a second-line treatment for KIT exon 11-mutated GISTs due to its activity against highly heterogeneous frequently occurring secondary mutations. This review summarizes current data on the use of ripretinib to treat advanced imatinib-resistant GISTs. We also propose future research directions to improve the targeted GIST treatment.

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瑞普替尼治疗晚期伊马替尼耐药性胃肠道间质瘤。
胃肠道间质瘤(GISTs)中KIT/PDGFRA酪氨酸激酶组成型激活的发现导致靶向药物伊马替尼的开发。然而,伊马替尼耐药性的不可避免的发展仍然是一个主要问题。瑞普替尼是一种新型靶向药物,可抑制广谱耐药KIT/PDGFRA突变体的活性。它于2020年获得批准,目前被主要国际指南推荐为晚期GIST的第四线及以上治疗。新出现的证据表明,里皮替尼作为KIT外显子11突变GIST的二线治疗药物优于舒尼替尼,因为它对高度异质性的频繁发生的二次突变具有活性。这篇综述总结了目前使用瑞普替尼治疗晚期伊马替尼耐药GIST的数据。我们还提出了改进靶向GIST治疗的未来研究方向。
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来源期刊
Journal of Digestive Diseases
Journal of Digestive Diseases 医学-胃肠肝病学
CiteScore
5.40
自引率
2.90%
发文量
81
审稿时长
6-12 weeks
期刊介绍: The Journal of Digestive Diseases is the official English-language journal of the Chinese Society of Gastroenterology. The journal is published twelve times per year and includes peer-reviewed original papers, review articles and commentaries concerned with research relating to the esophagus, stomach, small intestine, colon, liver, biliary tract and pancreas.
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