FLT3 Inhibitors: a paradigm for the development of targeted therapeutics for paediatric cancer

被引：48
作者：
Brown, P
Small, D
机构：
[1] Johns Hopkins, Sidney Kimmel Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA
[2] Johns Hopkins, Sidney Kimmel Canc Ctr, Dept Pediat, Baltimore, MD 21231 USA
来源：
EUROPEAN JOURNAL OF CANCER | 2004年 / 40卷 / 05期
关键词：
D O I：
10.1016/j.ejca.2003.08.030
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The area of molecularly-targeted cancer therapeutics is generating tremendous interest and excitement. While clinical investigation of these agents has been largely limited to adults, clinical trials for paediatric cancer patients with many of these agents are now underway. This paper reviews the current status of molecularly-targeted therapies for paediatric malignancies, with special attention given to one class of agents, inhibitors of the FLT3 receptor tyrosine kinase. FLT3 is expressed and activated in many human leukemias, including a significant percentage of pediatric AML and infant and childhood ALL, especially in the setting of MLL gene rearrangement. Activating mutations of FLT3 portend a poor prognosis in pediatric AML. Activated FLT3 can be effectively and selectively targeted by small molecule inhibitors, and these agents have shown promise in early phase clinical trials it adults with AML. Limited preclinical data with FLT3 inhibitors in MLL-rearranged ALL have also been reported. Challenges and future directions for the use of FLT3 inhibitors and other targeted agents in paediatric cancer are discussed. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码：707 / 721
页数：15
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