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靶向 Wnt/β-catenin 信号通路治疗胃肠道肿瘤:潜在进展。

Targeting the Wnt/β-catenin signal pathway for the treatment of gastrointestinal cancer: Potential for advancement.

机构信息

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Zhejiang University, Hangzhou, Zhejiang 310058, PR China; Innovation Institute for Artificial Intelligence in Medicine, Zhejiang University, Hangzhou, Zhejiang 310018, PR China.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.

出版信息

Biochem Pharmacol. 2024 Sep;227:116463. doi: 10.1016/j.bcp.2024.116463. Epub 2024 Aug 3.

DOI:10.1016/j.bcp.2024.116463
PMID:39102994
Abstract

Gastrointestinal cancers (GICs) are highly prevalent cancers that threaten human health worldwide. The Wnt/β-catenin signaling pathway has been reported to play a pivotal role in the carcinogenesis of GICs. Numerous interventions targeting the Wnt/β-catenin signaling in GICs are currently being tested in clinical trials with promising results. Unfortunately, there are no clinically approved drugs that effectively target this pathway. This comprehensive review aims to evaluate the impact of clinical therapies targeting the Wnt/β-catenin signaling pathway in GICs. By integrating data from bioinformatics databases and recent literature from the past five years, we examine the heterogeneous expression and regulatory mechanisms of Wnt/β-catenin pathway genes and proteins in GICs. Specifically, we focus on expression patterns, mutation frequencies, and clinical prognoses to understand their implications for treatment strategies. Additionally, we discuss recent clinical trial efforts targeting this pathway. Understanding the inhibitors currently under clinical investigation may help optimize foundational research and clinical strategies. We hope that elucidating the current status of precision therapeutic stratification for patients targeting the Wnt/β-catenin pathway will guide future innovations in precision medicine for GICs.

摘要

胃肠道癌症(GICs)是全球范围内严重威胁人类健康的高发癌症。已有研究报道 Wnt/β-catenin 信号通路在 GIC 的发生发展中起着关键作用。目前,许多针对 GIC 中 Wnt/β-catenin 信号通路的干预措施正在临床试验中进行测试,结果令人鼓舞。不幸的是,目前还没有经临床批准的有效靶向该通路的药物。本综述旨在评估靶向 Wnt/β-catenin 信号通路的临床疗法对 GIC 的影响。我们通过整合生物信息学数据库的数据和过去五年的最新文献,研究了 Wnt/β-catenin 通路基因和蛋白在 GIC 中的异质性表达和调控机制。具体来说,我们重点关注表达模式、突变频率和临床预后,以了解它们对治疗策略的影响。此外,我们还讨论了针对该通路的最新临床试验进展。了解目前正在进行的临床研究抑制剂可能有助于优化基础研究和临床策略。我们希望阐明目前针对 Wnt/β-catenin 通路的患者精准治疗分层的现状,将为胃肠道癌症的精准医学未来创新提供指导。

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