靶向mTOR信号通路及相关负反馈环治疗急性髓系白血病。
Targeting mTOR signaling pathways and related negative feedback loops for the treatment of acute myeloid leukemia.
作者信息
Carneiro Benedito A, Kaplan Jason B, Altman Jessica K, Giles Francis J, Platanias Leonidas C
机构信息
a Robert H Lurie Comprehensive Cancer Center of Northwestern University ; Chicago , IL , USA.
出版信息
Cancer Biol Ther. 2015;16(5):648-56. doi: 10.1080/15384047.2015.1026510.
Abstract
An accumulating understanding of the complex pathogenesis of acute myeloid leukemia (AML) continues to lead to promising therapeutic approaches. Among the key aberrant intracellular signaling pathways involved in AML, the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) axis is of major interest. This axis modulates a wide array of critical cellular functions, including proliferation, metabolism, and survival. Pharmacologic inhibitors of components of this pathway have been developed over the past decade, but none has an established role in the treatment of AML. This review will discuss the preclinical data and clinical results driving ongoing attempts to exploit the PI3K/AKT/mTOR pathway in patients with AML and address issues related to negative feedback loops that account for leukemic cell survival. Targeting the PI3K/AKT/mTOR pathway is of high interest for the treatment of AML, but combination therapies with other targeted agents may be needed to block negative feedback loops in leukemia cells.
摘要
对急性髓系白血病（AML）复杂发病机制的认识不断积累，持续催生着有前景的治疗方法。在AML涉及的关键异常细胞内信号通路中，磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素哺乳动物靶蛋白（PI3K/AKT/mTOR）轴备受关注。该轴调节一系列关键的细胞功能，包括增殖、代谢和存活。在过去十年中已开发出该通路成分的药理学抑制剂，但尚无一种在AML治疗中确立了作用。本综述将讨论推动当前在AML患者中利用PI3K/AKT/mTOR通路的临床前数据和临床结果，并探讨与白血病细胞存活相关的负反馈回路问题。靶向PI3K/AKT/mTOR通路在AML治疗中备受关注，但可能需要与其他靶向药物联合治疗以阻断白血病细胞中的负反馈回路。
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