砷：一种对 Hedgehog 驱动型癌症可能有用的毒药。
Arsenic: a potentially useful poison for Hedgehog-driven cancers.
机构信息
Department of Pediatrics, Weill Cornell Medical College, New York, New York 10065, USA.
出版信息
J Clin Invest. 2011 Jan;121(1):14-6. doi: 10.1172/JCI45692. Epub 2010 Dec 22.
Abstract
Dysregulated Hedgehog (Hh) signaling has been implicated in a growing number of human cancers. To date, most antagonists of this signaling pathway that have been developed target the Hh receptor Smoothened. However, these are predicted to have minimal effect when the pathway is activated as a result of dysregulation downstream of this receptor. In this issue of the JCI, Beauchamp and colleagues provide preclinical evidence that arsenic trioxide, a drug FDA approved for the treatment of acute promyelocytic leukemia, inhibits the growth of Ewing sarcoma and medulloblastoma cells by targeting GLI family zinc finger (GLI) proteins, which are Hh signaling pathway components downstream of Smoothened.
摘要
Hedgehog (Hh) 信号通路失调与越来越多种人类癌症相关。迄今为止，已开发出的大多数针对该信号通路的拮抗剂都以 Hh 受体 Smoothened 为靶点。然而，当该受体下游的失调导致该通路被激活时，这些拮抗剂预计效果甚微。在本期 JCI 中，Beauchamp 及其同事提供了临床前证据，表明三氧化二砷，一种经美国食品药品监督管理局批准用于治疗急性早幼粒细胞白血病的药物，通过靶向 Gli 家族锌指 (GLI) 蛋白抑制尤文肉瘤和髓母细胞瘤细胞的生长，GLI 蛋白是 Smoothened 下游的 Hh 信号通路成分。
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本文引用的文献
1
Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway.三氧化二砷通过阻断 Hedgehog/GLI 通路抑制人癌细胞生长和肿瘤在小鼠中的发展。
J Clin Invest. 2011 Jan;121(1):148-60. doi: 10.1172/JCI42874. Epub 2010 Dec 22.
2
Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector.砷通过阻止纤毛积累和降低Gli2 转录效应物的稳定性来拮抗 Hedgehog 通路。
Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13432-7. doi: 10.1073/pnas.1006822107. Epub 2010 Jul 12.
3
Arsenic trioxide - An old drug rediscovered.三氧化二砷——一种被重新发现的老药。
Blood Rev. 2010 Jul-Sep;24(4-5):191-9. doi: 10.1016/j.blre.2010.04.001. Epub 2010 May 15.
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New developments in the discovery of small molecule Hedgehog pathway antagonists.小分子 Hedgehog 通路拮抗剂发现的新进展。
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Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia.三氧化二砷为基础的单周期巩固化疗可避免急性早幼粒细胞白血病初始治疗中蒽环类药物的暴露。
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