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Targeting the Versatile Wnt/β-Catenin Pathway in Cancer Biology and Therapeutics: From Concept to Actionable Strategy.
OMICS: A Journal of Integrative Biology ( IF 3.3 ) Pub Date : 2019-10-15 , DOI: 10.1089/omi.2019.0147
Kevin Dzobo 1, 2 , Nicholas Ekow Thomford 3 , Dimakatso A Senthebane 1, 2
Affiliation  

This expert review offers a critical synthesis of the latest insights and approaches at targeting the Wnt/β-catenin pathway in various cancers such as colorectal cancer, melanoma, leukemia, and breast and lung cancers. Notably, from organogenesis to cancer, the Wnt/β-catenin signaling displays varied and highly versatile biological functions in animals, with virtually all tissues requiring the Wnt/β-catenin signaling in one way or the other. Aberrant expression of the members of the Wnt/β-catenin has been implicated in many pathological conditions, particularly in human cancers. Mutations in the Wnt/β-catenin pathway genes have been noted in diverse cancers. Biochemical and genetic data support the idea that inhibition of Wnt/β-catenin signaling is beneficial in cancer therapeutics. The interaction of this important pathway with other signaling systems is also noteworthy, but remains as an area for further research and discovery. In addition, formation of different complexes by components of the Wnt/β-catenin pathway and the precise roles of these complexes in the cytoplasmic milieu are yet to be fully elucidated. This article highlights the latest medical technologies in imaging, single-cell omics, use of artificial intelligence (e.g., machine learning techniques), genome sequencing, quantum computing, molecular docking, and computational softwares in modeling interactions between molecules and predicting protein-protein and compound-protein interactions pertinent to the biology and therapeutic value of the Wnt/β-catenin signaling pathway. We discuss these emerging technologies in relationship to what is currently needed to move from concept to actionable strategies in translating the Wnt/β-catenin laboratory discoveries to Wnt-targeted cancer therapies and diagnostics in the clinic.

中文翻译:

针对癌症生物学和治疗学中的多功能Wnt /β-Catenin途径:从概念到可行策略。

该专家综述提供了针对各种癌症(例如大肠癌,黑素瘤,白血病以及乳腺癌和肺癌)中针对Wnt /β-catenin途径的最新见解和方法的重要综述。值得注意的是,从器官发生到癌症,Wnt /β-catenin信号在动物中表现出多种多样且高度通用的生物学功能,几乎所有组织都以一种或另一种方式需要Wnt /β-catenin信号。Wnt /β-catenin成员的异常表达与许多病理状况有关,特别是在人类癌症中。Wnt /β-catenin途径基因中的突变已在多种癌症中被发现。生化和遗传数据支持这样的想法,即抑制Wnt /β-catenin信号传导在癌症治疗中是有益的。该重要途径与其他信号系统的相互作用也是值得注意的,但仍然是需要进一步研究和发现的领域。另外,由Wnt /β-连环蛋白途径的成分形成的不同复合物以及这些复合物在细胞质环境中的确切作用尚待充分阐明。本文重点介绍了最新的医学技术,包括成像,单细胞组学,人工智能的使用(例如机器学习技术),基因组测序,量子计算,分子对接以及在对分子之间的相互作用进行建模并预测蛋白质与蛋白质和与Wnt /β-catenin信号通路的生物学和治疗价值相关的化合物-蛋白质相互作用。
更新日期:2019-11-01
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