Targeting mTOR signaling pathways and related negative feedback loops for the treatment of acute myeloid leukemia

被引：37
作者：
Carneiro, Benedito A. [1 ,2 ,3 ]
Kaplan, Jason B. [1 ,2 ,3 ]
Altman, Jessica K. [1 ,2 ,3 ]
Giles, Francis J. [1 ,2 ,3 ]
Platanias, Leonidas C. [1 ,2 ,3 ,4 ]
机构：
[1] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
[2] Northwestern Univ, Feinberg Sch Med, Div Hematol & Oncol, Chicago, IL 60611 USA
[3] Northwestern Univ, Feinberg Sch Med, Northwestern Med Dev Therapeut Inst, Chicago, IL 60611 USA
[4] Jesse Brown VA Med Ctr, Div Hematol Oncol, Dept Med, Chicago, IL USA
来源：
CANCER BIOLOGY & THERAPY | 2015年 / 16卷 / 05期
基金：
美国国家卫生研究院;
关键词：
Acute myeloid leukemia; Akt; AML; MAPK; mTOR; PI3K; targeted therapy; ACUTE MYELOGENOUS LEUKEMIA; REFRACTORY HEMATOLOGIC MALIGNANCIES; ACUTE LYMPHOBLASTIC-LEUKEMIA; SMALL-MOLECULE INHIBITORS; NF-KAPPA-B; AKT-INHIBITOR; PHASE-I; CELL-PROLIFERATION; MAMMALIAN TARGET; KINASE INHIBITOR;
D O I：
10.1080/15384047.2015.1026510
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：648 / 656
页数：9
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