The Wnt pathway: emerging anticancer strategies.

Aman Gupta, Anukriti Verma, Ashutosh K Mishra, Gulshan Wadhwa, Sanjeev K Sharma, Chakresh K Jain
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引用次数: 26

Abstract

The canonical Wnt cascade has emerged as a critical regulator of cancer cells. Activation of the Wnt signaling pathway has also been associated with stem cell, thus raising the possibility of its role in embryogenesis and in the proliferation of malignant cancer cells. Wnt pathway has been reported to be involved in normal physiological processes in adult animals and integrally associated with cancer cell growth and maintenance, thus has been harnessed to devise strategies for anticancer therapy. The presence or absence of some members in this pathway, such as β-catenin, Axin or APC, has been found to involve in different types of tumors in human beings. Dysregulation of the canonical Wnt/β-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of β-catenin, has been implicated in colorectal tumorigenesis. Further, elevated levels of β-catenin protein, a hallmark of activated canonical Wnt pathway, have been significantly observed in common forms of human malignancies, indicating that activation of the Wnt pathway may play an important role in tumor development and hence could be a crucial consideration for drug development. The paper discusses the potential therapeutic and diagnostic strategies directing on Wnt pathways on the basis of recent patents and their analysis.

Wnt通路:新兴的抗癌策略
典型的Wnt级联已成为癌细胞的关键调节因子。Wnt信号通路的激活也与干细胞有关,从而提高了其在胚胎发生和恶性癌细胞增殖中的作用的可能性。据报道,Wnt通路参与成年动物的正常生理过程,并与癌细胞的生长和维持密切相关,因此已被用于制定抗癌治疗策略。该通路中某些成员的存在或缺失,如β-catenin、Axin或APC,已被发现与人类不同类型的肿瘤有关。典型的Wnt/β-catenin信号通路的失调,主要是通过APC肿瘤抑制基因的失活突变,或β-catenin的致癌突变,与结直肠癌的发生有关。此外,在常见的人类恶性肿瘤中显著观察到β-catenin蛋白(典型Wnt通路激活的标志)水平升高,这表明Wnt通路的激活可能在肿瘤发展中发挥重要作用,因此可能是药物开发的关键考虑因素。本文在最近专利及其分析的基础上,讨论了针对Wnt通路的潜在治疗和诊断策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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