• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

ETC-159，一种上游 Wnt 抑制剂，通过调节骨肉瘤中的血管生成诱导肿瘤坏死。

ETC-159, an Upstream Wnt inhibitor, Induces Tumour Necrosis via Modulation of Angiogenesis in Osteosarcoma.

机构信息

Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore.

Department of Orthopaedic Surgery, Singapore General Hospital, Singapore 169608, Singapore.

出版信息

Int J Mol Sci. 2023 Mar 1;24(5):4759. doi: 10.3390/ijms24054759.

DOI:10.3390/ijms24054759
PMID:36902186
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10003732/
Abstract

There is an increasing urgency in the search for new drugs to target high-grade cancers such as osteosarcomas (OS), as these have limited therapeutic options and poor prognostic outlook. Even though key molecular events leading to tumorigenesis are not well understood, it is widely agreed that OS tumours are Wnt-driven. ETC-159, a PORCN inhibitor that inhibits the extracellular secretion of Wnt, has recently progressed on to clinical trials. In vitro and in vivo murine and chick chorioallantoic membrane xenograft models were established to examine the effect of ETC-159 on OS. Consistent with our hypothesis, we noted that ETC-159 treatment not only resulted in markedly decreased β-catenin staining in xenografts, but also increased tumour necrosis and a significant reduction in vascularity-a hereby yet undescribed phenotype following ETC-159 treatment. Through further understanding the mechanism of this new window of vulnerability, therapies can be developed to potentiate and maximize the effectiveness of ETC-159, further increasing its clinical utility for the treatment of OS.

摘要

寻找针对骨肉瘤（OS）等高级别癌症的新药的紧迫性日益增加，因为这些癌症的治疗选择有限，预后不佳。尽管导致肿瘤发生的关键分子事件尚不清楚，但人们普遍认为 OS 肿瘤是 Wnt 驱动的。ETC-159 是一种 PORCN 抑制剂，可抑制 Wnt 的细胞外分泌，最近已进入临床试验阶段。建立了体外和体内鼠和鸡胚绒毛尿囊膜异种移植模型，以研究 ETC-159 对 OS 的影响。与我们的假设一致，我们注意到 ETC-159 治疗不仅导致异种移植物中 β-连环蛋白染色明显减少，而且还增加了肿瘤坏死和血管生成的显著减少——这是 ETC-159 治疗后尚未描述的表型。通过进一步了解这一新的脆弱性窗口的机制，可以开发出增强和最大化 ETC-159 有效性的疗法，进一步增加其在 OS 治疗中的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/0e9db859cafb/ijms-24-04759-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/4cae9ad5050a/ijms-24-04759-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/8670570df071/ijms-24-04759-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/26bc68f0434c/ijms-24-04759-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/0e9db859cafb/ijms-24-04759-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/4cae9ad5050a/ijms-24-04759-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/8670570df071/ijms-24-04759-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/26bc68f0434c/ijms-24-04759-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb1/10003732/0e9db859cafb/ijms-24-04759-g004.jpg

相似文献

1
ETC-159, an Upstream Wnt inhibitor, Induces Tumour Necrosis via Modulation of Angiogenesis in Osteosarcoma.ETC-159，一种上游 Wnt 抑制剂，通过调节骨肉瘤中的血管生成诱导肿瘤坏死。
Int J Mol Sci. 2023 Mar 1;24(5):4759. doi: 10.3390/ijms24054759.
2
β-Elemonic acid inhibits the growth of human Osteosarcoma through endoplasmic reticulum (ER) stress-mediated PERK/eIF2α/ATF4/CHOP activation and Wnt/β-catenin signal suppression.β-熊果苷通过内质网（ER）应激介导的 PERK/eIF2α/ATF4/CHOP 激活和 Wnt/β-连环蛋白信号抑制抑制人骨肉瘤的生长。
Phytomedicine. 2020 Apr;69:153183. doi: 10.1016/j.phymed.2020.153183. Epub 2020 Feb 7.
3
Dihydroartemisinin inhibits tumor growth of human osteosarcoma cells by suppressing Wnt/β-catenin signaling.二氢青蒿素通过抑制 Wnt/β-连环蛋白信号通路抑制人骨肉瘤细胞的生长。
Oncol Rep. 2013 Oct;30(4):1723-30. doi: 10.3892/or.2013.2658. Epub 2013 Aug 5.
4
Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/β-catenin signaling pathway.夹竹桃苷通过抑制Wnt/β-连环蛋白信号通路对骨肉瘤细胞的体外增殖、迁移和侵袭的抑制作用
J Exp Clin Cancer Res. 2015 Oct 6;34:115. doi: 10.1186/s13046-015-0232-8.
5
Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation.斑蝥素通过直接靶向 miR-214-3p/DKK3 轴抑制骨肉瘤增殖和转移，从而使 β-连环蛋白核易位和 LEF1 翻译失活。
Int J Biol Sci. 2021 Jun 16;17(10):2504-2522. doi: 10.7150/ijbs.51638. eCollection 2021.
6
Schisandrin B suppresses osteosarcoma lung metastasis by inhibiting the activation of the Wnt/β‑catenin and PI3K/Akt signaling pathways.五味子乙素通过抑制 Wnt/β-catenin 和 PI3K/Akt 信号通路的激活抑制骨肉瘤肺转移。
Oncol Rep. 2022 Mar;47(3). doi: 10.3892/or.2022.8261. Epub 2022 Jan 14.
7
Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/β-catenin signaling in human osteosarcoma cells.熊果酸通过抑制 Wnt/β-连环蛋白信号通路抑制人骨肉瘤细胞增殖并诱导其凋亡。
Int J Oncol. 2016 Nov;49(5):1973-1982. doi: 10.3892/ijo.2016.3701. Epub 2016 Sep 21.
8
Melittin inhibits lung metastasis of human osteosarcoma: Evidence of wnt/β-catenin signaling pathway participation.蜂毒素抑制人骨肉瘤肺转移：Wnt/β-连环蛋白信号通路参与的证据。
Toxicon. 2021 Jul 30;198:132-142. doi: 10.1016/j.toxicon.2021.04.024. Epub 2021 Apr 28.
9
miR-425-5p decreases LncRNA MALAT1 and TUG1 expressions and suppresses tumorigenesis in osteosarcoma via Wnt/β-catenin signaling pathway.miR-425-5p 通过 Wnt/β-catenin 信号通路降低骨肉瘤中 LncRNA MALAT1 和 TUG1 的表达并抑制肿瘤发生。
Int J Biochem Cell Biol. 2019 Jun;111:42-51. doi: 10.1016/j.biocel.2019.04.004. Epub 2019 Apr 12.
10
Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits Clear Cell Renal Cell Carcinoma.棘白菌素抑制剂 LGK974 下调 Wnt 信号通路并抑制肾透明细胞癌。
Biomed Res Int. 2020 Feb 13;2020:2527643. doi: 10.1155/2020/2527643. eCollection 2020.

引用本文的文献

1
Targeting Wnt-driven metabolic adaptations in cancer: integrating glycolysis, glutaminolysis, IDO1-mediated immune evasion, and therapeutic delivery strategies.靶向癌症中Wnt驱动的代谢适应性：整合糖酵解、谷氨酰胺分解、吲哚胺2,3-双加氧酶1介导的免疫逃逸及治疗递送策略
Front Cell Dev Biol. 2025 Aug 22;13:1622218. doi: 10.3389/fcell.2025.1622218. eCollection 2025.
2
Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Wnt/β-连环蛋白介导的癌症信号通路：最新进展及其在癌症治疗中的应用
Mol Cancer. 2025 Jun 10;24(1):171. doi: 10.1186/s12943-025-02363-1.
3
Signaling pathways in liver cancer: pathogenesis and targeted therapy.

本文引用的文献

1
Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment.多组学分析确定了具有不同预后的骨肉瘤亚型，提示分层治疗。
Nat Commun. 2022 Nov 23;13(1):7207. doi: 10.1038/s41467-022-34689-5.
2
Apatinib Functioned as Tumor Suppressor of Synovial Sarcoma through Regulating miR-34a-5p/HOXA13 Axis.阿帕替尼通过调控 miR-34a-5p/HOXA13 轴发挥滑膜肉瘤肿瘤抑制作用。
Comput Math Methods Med. 2022 Oct 12;2022:7214904. doi: 10.1155/2022/7214904. eCollection 2022.
3
The Heterogeneity of Osteosarcoma: The Role Played by Cancer Stem Cells.
肝癌信号通路：发病机制与靶向治疗。
Mol Biomed. 2024 May 31;5(1):20. doi: 10.1186/s43556-024-00184-0.
4
Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights into Disease Progression and Therapeutic Targets.结直肠癌肿瘤基质的细胞和分子机制：对疾病进展及治疗靶点的见解
Biomedicines. 2023 Aug 23;11(9):2361. doi: 10.3390/biomedicines11092361.
骨肉瘤的异质性：肿瘤干细胞的作用。
Adv Exp Med Biol. 2019;1139:187-200. doi: 10.1007/978-3-030-14366-4_11.
4
Targeting the Wnt/β-catenin pathway in human osteosarcoma cells.靶向人类骨肉瘤细胞中的Wnt/β-连环蛋白信号通路。
Oncotarget. 2018 Dec 4;9(95):36780-36792. doi: 10.18632/oncotarget.26377.
5
Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy.同时进行阿仑膦酸盐治疗可减轻因Wnt抑制导致的骨质流失。
Bone Res. 2018 May 25;6:17. doi: 10.1038/s41413-018-0017-8. eCollection 2018.
6
δ-Catenin promotes tumorigenesis and metastasis of lung adenocarcinoma.δ-连环蛋白促进肺腺癌的肿瘤发生和转移。
Oncol Rep. 2018 Feb;39(2):809-817. doi: 10.3892/or.2017.6140. Epub 2017 Dec 8.
7
Downregulation of 14-3-3β inhibits proliferation and migration in osteosarcoma cells.14-3-3β 的下调抑制骨肉瘤细胞的增殖和迁移。
Mol Med Rep. 2018 Feb;17(2):2493-2500. doi: 10.3892/mmr.2017.8144. Epub 2017 Nov 22.
8
Targeting signaling pathways in multiple myeloma: Pathogenesis and implication for treatments.靶向多发性骨髓瘤的信号通路：发病机制及治疗意义。
Cancer Lett. 2018 Feb 1;414:214-221. doi: 10.1016/j.canlet.2017.11.020. Epub 2017 Nov 22.
9
IWR-1, a tankyrase inhibitor, attenuates Wnt/β-catenin signaling in cancer stem-like cells and inhibits in vivo the growth of a subcutaneous human osteosarcoma xenograft.IWR-1，一种端锚聚合酶抑制剂，可减弱癌症干细胞样细胞中的 Wnt/β-catenin 信号通路，并抑制皮下人骨肉瘤异种移植物的生长。
Cancer Lett. 2018 Feb 1;414:1-15. doi: 10.1016/j.canlet.2017.11.004. Epub 2017 Nov 8.
10
miR-135b Stimulates Osteosarcoma Recurrence and Lung Metastasis via Notch and Wnt/β-Catenin Signaling.微小RNA-135b通过Notch和Wnt/β-连环蛋白信号通路促进骨肉瘤复发和肺转移。
Mol Ther Nucleic Acids. 2017 Sep 15;8:111-122. doi: 10.1016/j.omtn.2017.06.008. Epub 2017 Jun 15.