文章：

WNT信号通路作为癌症治疗靶点

WNT signalling pathways as therapeutic targets in cancer

原文发布日期：2012-12-21

DOI: 10.1038/nrc3419

类型: Review Article

开放获取: 否

要点：

1. WNTs are secreted glycoproteins that regulate multiple signalling pathways through both β-catenin (CTNNB1)-dependent and CTNNB1–independent mechanisms.
2. The activation of WNT signalling pathways can be both positively and negatively correlated with patient outcomes in different types of cancer.
3. WNT–CTNNB1 signalling can either promote or inhibit tumour initiation, growth, metastases and drug resistance in a cancer-stage-specific and a cancer-type-specific manner.
4. CTNNB1-independent WNT signalling pathways also contribute to tumorigenesis and cancer progression in a context-dependent manner.
5. Aberrations in WNT signalling pathways and alterations in other oncogene and tumour suppressor pathways cooperate to drive cancer initiation and progression.
6. Multiple strategies for targeting WNT signalling — ranging from small molecules to blocking antibodies, and peptide agonists and antagonists — are now in development, thus paving the way for initial clinical trials using WNT modulators in cancer patients.

要点翻译：

1. WNTs是分泌型糖蛋白，通过β-连环蛋白（CTNNB1）依赖性和CTNNB1非依赖性机制调控多种信号通路。
2. 在不同类型癌症中，WNT信号通路的激活与患者预后既可能呈正相关，也可能呈负相关。
3. WNT-CTNNB1信号通路以癌症阶段特异性和癌症类型特异性的方式，既可促进也可抑制肿瘤发生、生长、转移及耐药性。
4. CTNNB1非依赖性WNT信号通路同样会以环境依赖性方式参与肿瘤发生和癌症进展。
5. WNT信号通路的异常与其他癌基因和肿瘤抑制通路的改变共同驱动癌症的发生发展。
6. 目前正在开发多种靶向WNT信号的策略——包括小分子药物、阻断抗体、肽类激动剂和拮抗剂——这为在癌症患者中开展WNT调节剂的初步临床试验铺平了道路。

英文摘要：

Since the initial discovery of the oncogenic activity of WNT1 in mouse mammary glands, our appreciation for the complex roles for WNT signalling pathways in cancer has increased dramatically. WNTs and their downstream effectors regulate various processes that are important for cancer progression, including tumour initiation, tumour growth, cell senescence, cell death, differentiation and metastasis. Although WNT signalling pathways have been difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can alter WNT signalling in preclinical models, thus setting the stage for clinical trials in humans.

摘要翻译： 

自WNT1在小鼠乳腺中的致癌活性首次被发现以来，我们对WNT信号通路在癌症中复杂作用的认识已显著加深。WNT及其下游效应分子调控着肿瘤发生、生长、衰老、死亡、分化和转移等多个癌症进展关键环节。尽管WNT通路难以靶向，但改进的药物发现平台与新技术已推动临床前模型中可干预WNT信号的活性剂问世，为人类临床试验铺平道路。

原文链接：

WNT signalling pathways as therapeutic targets in cancer