Nuclear Receptors as Potential Therapeutic Targets for Myeloid Leukemia.
Nuclear Receptors as Potential Therapeutic Targets for Myeloid Leukemia.
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作者：
Pan P;Chen X
核受体（NR）超家族在许多实体肿瘤中得到了广泛的研究，一些受体已成为开发治疗的靶点。然而，它们在白血病中的作用尚不清楚，并且在不同类型的白血病中差异很大。一些NRs参与介导髓细胞的分化，使其成为髓性白血病有吸引力的治疗靶点。迄今为止，全反式维甲酸（ATRA）治疗急性早幼粒细胞白血病（APL）的成功仍然是癌症分化治疗的经典和无与伦比的例子。ATRA靶向视黄酸受体（RAR），促进白血病细胞分化和/或凋亡。此外，维生素D受体（VDR）和过氧化物酶体增殖激活受体（PPAR）的配体/激动剂也被证明可以抑制白血病细胞的增殖、诱导分化和促进细胞凋亡。令人鼓舞的是，联合使用不同的NR激动剂或在化疗中添加NR激动剂已显示出一些协同抗白血病作用。本文将对近年来的研究成果进行综述，并讨论选定的NRs在急慢性髓系白血病中的治疗潜力，重点是RAR、VDR、PPAR和类视黄醇X受体（RXR）。我们相信，在这一领域开展更多的机制研究，不仅将为NRs在白血病中的作用提供新的思路，而且还将进一步扩大现有靶向NRs治疗药物的临床应用。
The nuclear receptor (NR) superfamily has been studied extensively in many solid tumors and some receptors have been targeted to develop therapies. However, their roles in leukemia are less clear and vary considerably among different types of leukemia. Some NRs participate in mediating the differentiation of myeloid cells, making them attractive therapeutic targets for myeloid leukemia. To date, the success of all-trans retinoic acid (ATRA) in treating acute promyelocytic leukemia (APL) remains a classical and unsurpassable example of cancer differentiation therapy. ATRA targets retinoic acid receptor (RAR) and forces differentiation and/or apoptosis of leukemic cells. In addition, ligands/agonists of vitamin D receptor (VDR) and peroxisome proliferator-activated receptor (PPAR) have also been shown to inhibit proliferation, induce differentiation, and promote apoptosis of leukemic cells. Encouragingly, combining different NR agonists or the addition of NR agonists to chemotherapies have shown some synergistic anti-leukemic effects. This review will summarize recent research findings and discuss the therapeutic potential of selected NRs in acute and chronic myeloid leukemia, focusing on RAR, VDR, PPAR, and retinoid X receptor (RXR). We believe that more mechanistic studies in this field will not only shed new lights on the roles of NRs in leukemia, but also further expand the clinical applications of existing therapeutic agents targeting NRs.
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DOI：
10.1016/s1470-2045(14)70281-5
发表时间：
2014-08
期刊：
The Lancet. Oncology
影响因子：
--
作者：
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影响因子：
45.3
作者：
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通讯作者：
Milligan, Donald
影响因子：
45.3
作者：
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Wheatley, Keith
DOI：
10.1161/atvbaha.109.191189
发表时间：
2010-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
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作者：
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通讯作者：
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影响因子：
8.5
作者：
Hu, X. T.;Zuckerman, K. S.
通讯作者：
Zuckerman, K. S.