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急性髓系白血病的靶向治疗:聚焦于FLT-3抑制剂和ABT199。

Targeted therapies in Acute Myeloid Leukemia: a focus on FLT-3 inhibitors and ABT199.

作者信息

Naqvi Kiran, Konopleva Marina, Ravandi Farhad

机构信息

a Department of Leukemia , University of Texas, MD Anderson Cancer Center , Houston , TX , USA.

出版信息

Expert Rev Hematol. 2017 Oct;10(10):863-874. doi: 10.1080/17474086.2017.1366852. Epub 2017 Aug 21.

Abstract

Acute myeloid leukemia (AML) remains a therapeutic challenge. Despite ongoing research, the standard therapy for AML has not changed significantly in the past four decades. With the identification of cytogenetic and molecular abnormalities, several promising therapeutic agents are currently being investigated. FLT3 mutation is a well-recognized target seen in 30% of the cytogenetically normal AML. More recently, the BCL2 family of anti-apoptotic proteins have also generated great interest as a therapeutic target. Areas covered: This review will cover the role of FLT3 inhibitors in AML, discussing trials in relapsed/refractory AML and in the frontline setting, including the young and elderly patient population. Toxicities and potential mechanism of resistance will also be covered. In addition, most current studies demonstrating the role of BCL-2 inhibitors namely ABT-199/venetoclax in AML will also be discussed. Expert commentary: AML is one of the most heterogeneous group of hematological malignancies. It remains a therapeutic challenge with limited therapeutic progress despite ongoing research. With the identification of different mutations in AML, several drugs are being evaluated in clinical trials. Targeted agents such as FLT3 inhibitors and BH3 mimetics so far have shown promising results in terms of response and toxicity profile.

摘要

急性髓系白血病(AML)仍然是一个治疗难题。尽管研究不断,但在过去四十年里,AML的标准治疗方法并未发生显著变化。随着细胞遗传学和分子异常的发现,目前正在研究几种有前景的治疗药物。FLT3突变是一种在30%细胞遗传学正常的AML中常见的公认靶点。最近,抗凋亡蛋白的BCL2家族作为治疗靶点也引起了极大关注。涵盖领域:本综述将涵盖FLT3抑制剂在AML中的作用,讨论复发/难治性AML以及一线治疗中的试验,包括年轻和老年患者群体。还将涵盖毒性和潜在的耐药机制。此外,还将讨论目前大多数证明BCL-2抑制剂即ABT-199/维奈托克在AML中作用的研究。专家评论:AML是血液系统恶性肿瘤中异质性最强的类型之一。尽管研究不断,但它仍然是一个治疗难题,治疗进展有限。随着AML中不同突变的发现,几种药物正在临床试验中进行评估。到目前为止,FLT3抑制剂和BH3模拟物等靶向药物在反应和毒性方面已显示出有前景的结果。

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