Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia.
Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia.
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DOI：
10.3389/fped.2017.00248
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发表时间：
2017
影响因子：
2.6
通讯作者：
Tasian SK
中科院分区：
文献类型：
--
作者：
Sexauer AN;Tasian SK
急性髓性白血病（AML）是儿童期第二常见的白血病，与高化疗耐药率和复发率相关。最大强度多药化疗治疗的AML儿童的临床结局远远落后于更常见的急性淋巴细胞白血病儿童，表明持续需要新的治疗方法来降低复发风险并改善长期生存率。FMS样酪氨酸激酶-3受体基因（FLT 3）突变发生在约25%的儿童和成人AML患者中，并与特别差的预后相关。靶向FLT 3抑制剂的鉴定和开发代表了AML患者治疗中的重大精准医学范式转变。虽然许多第一代FLT 3抑制剂的进一步开发受到有限效力和由于对其他激酶的影响而产生的显著毒性的阻碍，但更具选择性的第二代和第三代FLT 3抑制剂在复发性/难治性和现在新发FLT 3突变的AML环境中表现出优异的耐受性和显著的疗效。虽然这些最新和最有前途的抑制剂主要在成人人群中进行了研究，但最近正在进行或计划进行FLT 3抑制剂与化疗的儿科研究。成功开发基于FLT 3转运蛋白的疗法对于改善这种高危AML亚型儿童的预后至关重要。
Acute myeloid leukemia (AML) is the second most common leukemia of childhood and is associated with high rates of chemotherapy resistance and relapse. Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival. Mutations in the FMS-like tyrosine kinase-3 receptor gene (FLT3) occur in approximately 25% of children and adults with AML and are associated with particularly poor prognoses. Identification and development of targeted FLT3 inhibitors represents a major precision medicine paradigm shift in the treatment of patients with AML. While further development of many first-generation FLT3 inhibitors was hampered by limited potency and significant toxicity due to effects upon other kinases, the more selective second- and third-generation FLT3 inhibitors have demonstrated excellent tolerability and remarkable efficacy in the relapsed/refractory and now de novo FLT3-mutated AML settings. While these newest and most promising inhibitors have largely been studied in the adult population, pediatric investigation of FLT3 inhibitors with chemotherapy is relatively recently ongoing or planned. Successful development of FLT3 inhibitor-based therapies will be essential to improve outcomes in children with this high-risk subtype of AML.
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影响因子：
6.2
作者：
Alvarado, Yesid;Kantarjian, Hagop M.;Luthra, Rajyalakshmi;Ravandi, Farhad;Borthakur, Gautam;Garcia-Manero, Guillermo;Konopleva, Marina;Estrov, Zeev;Andreeff, Michael;Cortes, Jorge E.
通讯作者：
Cortes, Jorge E.
影响因子：
158.5
作者：
Druker, Brian J.;Guilhot, Francois;Larson, Richard A.
通讯作者：
Larson, Richard A.
影响因子：
6.2
作者：
Bernstein, Mark L.
通讯作者：
Bernstein, Mark L.
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