用于癌症靶向治疗的 WNT 信号通路小分子抑制剂:WNT、自噬和细胞凋亡之间的相互作用。

IF 4.2 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Nayana A Menon, Chethana D Kumar, Pournami Ramachandran, Britny Blaize, Mridul Gautam, Marco Cordani, Lekha Dinesh Kumar
{"title":"用于癌症靶向治疗的 WNT 信号通路小分子抑制剂:WNT、自噬和细胞凋亡之间的相互作用。","authors":"Nayana A Menon, Chethana D Kumar, Pournami Ramachandran, Britny Blaize, Mridul Gautam, Marco Cordani, Lekha Dinesh Kumar","doi":"10.1016/j.ejphar.2024.177137","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer represents an intricate and heterogeneous ailment that evolves from a multitude of epigenetic and genetic variations that disrupt normal cellular function. The WNT/β-catenin pathway is an essential one in maintaining the balance between cell renewal and differentiation in various tissues. Abnormal activation of this pathway can lead to uncontrolled cell growth and initiate cancer across a variety of tissues such as the colon, skin, liver, and ovary. It enhances characteristics that lead to cancer progression, including angiogenesis, invasion and metastasis. Processes like autophagy and apoptosis which regulate cell death and play a crucial role in maintaining cellular equilibrium are also intimately linked with WNT- β-catenin pathway. Thus, targeting WNT pathway has become a key strategy in developing antitumor therapies. Employing s has emerged as a targeted therapies to improve the clinical outcome compared to conventional cancer treatments. Many strategies for using small molecule inhibitors for modulating the WNT/β-catenin pathway, such as hindering WNT ligands' secretion or interaction, disrupting receptor complex, and blocking the nuclear translocation of β-catenin have been investigated. These interventions have shown promise in both preclinical and clinical settings. This review provides a comprehensive understanding of the role of WNT/β-catenin signalling pathway's role in cancer, emphasizing its regulation of autophagy and apoptosis. Our goal is to highlight the potential of specific small molecule inhibitors targeting this pathway, fostering the development of novel, tailored cancer treatments.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177137"},"PeriodicalIF":4.2000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Small-Molecule Inhibitors in WNT Signalling Pathway for Targeted Cancer Therapy: Interplay between WNT, Autophagy and Apoptosis.\",\"authors\":\"Nayana A Menon, Chethana D Kumar, Pournami Ramachandran, Britny Blaize, Mridul Gautam, Marco Cordani, Lekha Dinesh Kumar\",\"doi\":\"10.1016/j.ejphar.2024.177137\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cancer represents an intricate and heterogeneous ailment that evolves from a multitude of epigenetic and genetic variations that disrupt normal cellular function. The WNT/β-catenin pathway is an essential one in maintaining the balance between cell renewal and differentiation in various tissues. Abnormal activation of this pathway can lead to uncontrolled cell growth and initiate cancer across a variety of tissues such as the colon, skin, liver, and ovary. It enhances characteristics that lead to cancer progression, including angiogenesis, invasion and metastasis. Processes like autophagy and apoptosis which regulate cell death and play a crucial role in maintaining cellular equilibrium are also intimately linked with WNT- β-catenin pathway. Thus, targeting WNT pathway has become a key strategy in developing antitumor therapies. Employing s has emerged as a targeted therapies to improve the clinical outcome compared to conventional cancer treatments. Many strategies for using small molecule inhibitors for modulating the WNT/β-catenin pathway, such as hindering WNT ligands' secretion or interaction, disrupting receptor complex, and blocking the nuclear translocation of β-catenin have been investigated. These interventions have shown promise in both preclinical and clinical settings. This review provides a comprehensive understanding of the role of WNT/β-catenin signalling pathway's role in cancer, emphasizing its regulation of autophagy and apoptosis. Our goal is to highlight the potential of specific small molecule inhibitors targeting this pathway, fostering the development of novel, tailored cancer treatments.</p>\",\"PeriodicalId\":12004,\"journal\":{\"name\":\"European journal of pharmacology\",\"volume\":\" \",\"pages\":\"177137\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-11-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European journal of pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ejphar.2024.177137\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ejphar.2024.177137","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

癌症是一种错综复杂的异质性疾病,由多种破坏正常细胞功能的表观遗传和基因变异演变而来。WNT/β-catenin 通路是维持各种组织中细胞更新和分化之间平衡的重要通路。该通路的异常激活会导致细胞生长失控,并在结肠、皮肤、肝脏和卵巢等多种组织中引发癌症。它增强了导致癌症进展的特征,包括血管生成、侵袭和转移。自噬和细胞凋亡等过程可调节细胞死亡并在维持细胞平衡方面发挥关键作用,它们也与 WNT-β-catenin 通路密切相关。因此,靶向 WNT 通路已成为开发抗肿瘤疗法的关键策略。与传统的癌症治疗方法相比,小分子靶向药物已成为一种可改善临床疗效的靶向疗法。利用小分子抑制剂调节 WNT/β-catenin 通路的策略有很多,如阻碍 WNT 配体的分泌或相互作用、破坏受体复合物、阻断 β-catenin 的核转位等。这些干预措施已在临床前和临床环境中显示出前景。本综述全面介绍了 WNT/β-catenin 信号通路在癌症中的作用,强调了它对自噬和细胞凋亡的调控作用。我们的目标是强调靶向该通路的特异性小分子抑制剂的潜力,从而促进新型定制癌症治疗方法的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Small-Molecule Inhibitors in WNT Signalling Pathway for Targeted Cancer Therapy: Interplay between WNT, Autophagy and Apoptosis.

Cancer represents an intricate and heterogeneous ailment that evolves from a multitude of epigenetic and genetic variations that disrupt normal cellular function. The WNT/β-catenin pathway is an essential one in maintaining the balance between cell renewal and differentiation in various tissues. Abnormal activation of this pathway can lead to uncontrolled cell growth and initiate cancer across a variety of tissues such as the colon, skin, liver, and ovary. It enhances characteristics that lead to cancer progression, including angiogenesis, invasion and metastasis. Processes like autophagy and apoptosis which regulate cell death and play a crucial role in maintaining cellular equilibrium are also intimately linked with WNT- β-catenin pathway. Thus, targeting WNT pathway has become a key strategy in developing antitumor therapies. Employing s has emerged as a targeted therapies to improve the clinical outcome compared to conventional cancer treatments. Many strategies for using small molecule inhibitors for modulating the WNT/β-catenin pathway, such as hindering WNT ligands' secretion or interaction, disrupting receptor complex, and blocking the nuclear translocation of β-catenin have been investigated. These interventions have shown promise in both preclinical and clinical settings. This review provides a comprehensive understanding of the role of WNT/β-catenin signalling pathway's role in cancer, emphasizing its regulation of autophagy and apoptosis. Our goal is to highlight the potential of specific small molecule inhibitors targeting this pathway, fostering the development of novel, tailored cancer treatments.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
期刊介绍: The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信