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靶向刺猬信号通路的抗癌药物研发。

Development of anticancer agents targeting the Hedgehog signaling.

作者信息

Zhang Xiangqian, Tian Ye, Yang Yanling, Hao Jijun

机构信息

College of Life Science, Yan'an University, Yan'an, 716000, Shaanxi, China.

Medical College, Yan'an University, Yan'an, 716000, Shaanxi, China.

出版信息

Cell Mol Life Sci. 2017 Aug;74(15):2773-2782. doi: 10.1007/s00018-017-2497-x. Epub 2017 Mar 17.

DOI:10.1007/s00018-017-2497-x
PMID:28314894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11107598/
Abstract

Hedgehog signaling is an evolutionarily conserved pathway which is essential in embryonic and postnatal development as well as adult organ homeostasis. Abnormal regulation of Hedgehog signaling is implicated in many diseases including cancer. Consequently, substantial efforts have made in the past to develop potential therapeutic agents that specifically target the Hedgehog signaling for cancer treatment. Here, we review the therapeutic agents for inhibition of the Hedgehog signaling and their clinical advances in cancer treatment.

摘要

刺猬信号通路是一条在进化上保守的信号通路，在胚胎发育、出生后发育以及成体器官稳态维持中至关重要。刺猬信号通路的异常调控与包括癌症在内的多种疾病相关。因此，过去人们付出了巨大努力来开发特异性靶向刺猬信号通路用于癌症治疗的潜在治疗药物。在此，我们综述了抑制刺猬信号通路的治疗药物及其在癌症治疗中的临床进展。

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Development of anticancer agents targeting the Hedgehog signaling.靶向刺猬信号通路的抗癌药物研发。
Cell Mol Life Sci. 2017 Aug;74(15):2773-2782. doi: 10.1007/s00018-017-2497-x. Epub 2017 Mar 17.
2
Discovery of Hedgehog Antagonists for Cancer Therapy.用于癌症治疗的刺猬信号通路拮抗剂的发现。
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Hedgehog Signaling: From Basic Biology to Cancer Therapy.刺猬信号通路：从基础生物学到癌症治疗
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Cancer stem cells as a target population for drug discovery.癌症干细胞作为药物研发的目标群体。
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Targeting Hedgehog signaling pathway: Paving the road for cancer therapy.靶向 Hedgehog 信号通路：为癌症治疗铺平道路。
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Small-molecule inhibitors of the hedgehog signaling pathway as cancer therapeutics. hedgehog 信号通路小分子抑制剂作为癌症治疗药物。
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The role of Hedgehog and Notch signaling pathway in cancer.刺猬信号通路和Notch信号通路在癌症中的作用。
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Gemcitabine-induced Gli-dependent activation of hedgehog pathway resists to the treatment of urothelial carcinoma cells.吉西他滨诱导的Gli 依赖性 Hedgehog 通路激活抵抗尿路上皮癌细胞的治疗。
PLoS One. 2021 Jul 8;16(7):e0254011. doi: 10.1371/journal.pone.0254011. eCollection 2021.
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A Smo/Gli Multitarget Hedgehog Pathway Inhibitor Impairs Tumor Growth.一种Smo/Gli多靶点刺猬信号通路抑制剂可抑制肿瘤生长。
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Design of Hedgehog pathway inhibitors for cancer treatment.癌症治疗中 Hedgehog 信号通路抑制剂的设计。
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Bone marrow mesenchymal stromal cells attenuate silica-induced pulmonary fibrosis potentially by attenuating Wnt/β-catenin signaling in rats.骨髓间充质基质细胞通过减轻大鼠 Wnt/β-catenin 信号通路减轻二氧化硅诱导的肺纤维化。
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本文引用的文献

1
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.刺猬酰基转移酶抑制剂的表征确定了一种癌细胞用于刺猬信号传导的小分子探针。
ACS Chem Biol. 2016 Dec 16;11(12):3256-3262. doi: 10.1021/acschembio.6b00896. Epub 2016 Oct 25.
2
The hedgehog pathway in triple-negative breast cancer.三阴性乳腺癌中的刺猬信号通路。
Cancer Med. 2016 Oct;5(10):2989-3006. doi: 10.1002/cam4.833. Epub 2016 Aug 18.
3
Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells.小分子刺猬因子抑制剂可减弱急性髓系白血病细胞的白血病起始潜能。
Cancer Sci. 2016 Oct;107(10):1422-1429. doi: 10.1111/cas.13019. Epub 2016 Sep 2.
4
Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.靶向音猬因子信号通路：对Smoothened和GLI抑制剂的综述
Cancers (Basel). 2016 Feb 15;8(2):22. doi: 10.3390/cancers8020022.
5
Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study.口服平滑肌瘤拮抗剂PF-04449913治疗髓系恶性肿瘤患者：1期安全性和药代动力学研究。
Lancet Haematol. 2015 Aug;2(8):e339-46. doi: 10.1016/S2352-3026(15)00096-4. Epub 2015 Jul 26.
6
An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib.一项研究者发起的关于索尼德吉治疗对维莫德吉耐药的晚期基底细胞癌患者的开放标签试验。
Clin Cancer Res. 2016 Mar 15;22(6):1325-9. doi: 10.1158/1078-0432.CCR-15-1588. Epub 2015 Nov 6.
7
Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma.磷酸二酯酶4D在神经纤毛蛋白下游发挥作用，以控制刺猬信号转导和髓母细胞瘤的生长。
Elife. 2015 Sep 15;4:e07068. doi: 10.7554/eLife.07068.
8
Apremilast (Otezla): A New Oral Treatment for Adults With Psoriasis and Psoriatic Arthritis.阿普米司特（欧泰乐）：一种用于成人银屑病和银屑病关节炎的新型口服治疗药物。
P T. 2015 Aug;40(8):495-500.
9
Targeting the Hedgehog signaling pathway in cancer: beyond Smoothened.靶向癌症中的刺猬信号通路：超越 smoothened 蛋白
Oncotarget. 2015 Jun 10;6(16):13899-913. doi: 10.18632/oncotarget.4224.
10
Synergistic inhibition of colon carcinoma cell growth by Hedgehog-Gli1 inhibitor arsenic trioxide and phosphoinositide 3-kinase inhibitor LY294002.砷剂三氧化二砷和磷脂酰肌醇 3-激酶抑制剂 LY294002 协同抑制结肠癌细胞生长。
Onco Targets Ther. 2015 Apr 17;8:877-83. doi: 10.2147/OTT.S71034. eCollection 2015.