Investigational FMS-like tyrosine kinase 3 inhibitors in treatment of acute myeloid leukemia.
Investigational FMS-like tyrosine kinase 3 inhibitors in treatment of acute myeloid leukemia.
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DOI：
10.1517/13543784.2014.911839
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发表时间：
2014-07
影响因子：
6.1
通讯作者：
Ravandi F
中科院分区：
文献类型：
--
作者：
Pemmaraju N;Kantarjian H;Andreeff M;Cortes J;Ravandi F
大多数急性髓系白血病 (AML) 患者的预后仍然不佳。在过去的十年中，人们对 AML 发病机制的细胞遗传学和分子决定因素的理解取得了重大进展。其中一项进展是识别 FMS 样酪氨酸激酶 3 基因 (FLT3) 中的重复突变。目前，这一标志物出现在大约三分之一的 AML 患者中，表明预后较差，但也确定了重要的治疗靶点。 FLT3激酶抑制剂现已作为单一药物和与化疗药物联合进行I、II和III期临床试验的临床评估。不幸的是，迄今为止，还没有一种 FLT3 抑制剂获得 FDA 批准用于治疗 AML 患者。然而，有几种有前途的 FLT3 抑制剂正在药物开发的各个阶段进行评估。本次审查旨在突出那些在发展中走得最远的代理。它还关注那些正在与其他抗白血病药物联合评估的 FLT3 抑制剂。作者认为，尽管该亚组 AML 患者的预后历来较差，但 FLT3 抑制剂的研究领域仍然充满希望。最有前途的研究领域可能是阐明 FLT3 抑制剂的耐药机制，以及单独开发有效的 FLT3 抑制剂，或与低甲基化药物、细胞毒性化疗或其他靶向药物联合开发。
Outcomes for the majority of patients with Acute Myeloid Leukemia (AML) remain poor. Over the past decade, significant progress has been made in the understanding of the cytogenetic and molecular determinants of AML pathogenesis. One such advance is the identification of recurring mutations in the FMS-like tyrosine kinase 3 gene(FLT3). Currently, this marker, which appears in approximately one third of all AML patients, signifies a poorer prognosis, but also identifies an important target for therapy. FLT3 kinase inhibitors have now undergone clinical evaluation in phase I, II and III clinical trials, as both single agents and in combination with chemotherapeutics. Unfortunately, to date, none of the FLT3 inhibitors have gained FDA approval for the treatment of patients with AML. Yet, there are several promising FLT3 inhibitors are being evaluated in all phases of drug development. This review aims to highlight the agents furthest along in their development. It also focuses on those FLT3 inhibitors that are being evaluated in combination with other anti-leukemia agents. The authors believe that the field of research for FLT3 inhibitors remains promising, despite the historically poor prognosis of this subgroup of patients with AML. The most promising areas of research will likely be the elucidation of the mechanisms of resistance to FLT3 inhibitors, and development of potent FLT3 inhibitors alone, or in cominbation with hypomethylating agents, cytotoxic chemotherapy, or with other targeted agents.
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影响因子：
20.3
作者：
Barry, Elly V.;Clark, Jennifer J.;Gilliland, D. Gary
通讯作者：
Gilliland, D. Gary
影响因子：
37.3
作者：
Chen, Weina;Drakos, Elias;Rassidakis, George Z.
通讯作者：
Rassidakis, George Z.
影响因子：
5.7
作者：
Gozgit JM;Wong MJ;Wardwell S;Tyner JW;Loriaux MM;Mohemmad QK;Narasimhan NI;Shakespeare WC;Wang F;Druker BJ;Clackson T;Rivera VM
通讯作者：
Rivera VM
影响因子：
45.3
作者：
Cortes, Jorge E.;Kantarjian, Hagop;Levis, Mark
通讯作者：
Levis, Mark
DOI：
10.1158/1078-0432.ccr-13-1323
发表时间：
2013-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Baker SD;Zimmerman EI;Wang YD;Orwick S;Zatechka DS;Buaboonnam J;Neale GA;Olsen SR;Enemark EJ;Shurtleff S;Rubnitz JE;Mullighan CG;Inaba H
通讯作者：
Inaba H