Javadinia Seyed Alireza, Shahidsales Soodabeh, Fanipakdel Azar, Joudi-Mashhad Mona, Mehramiz Mehrane, Talebian Sahar, Maftouh Mona, Mardani Ramin, Hassanian Seyed Mahdi, Khazaei Majid, Ferns Gordon A, Avan Amir
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Biochem. 2019 May;120(5):6833-6840. doi: 10.1002/jcb.27835. Epub 2018 Oct 28.
The Wnt/β-catenin pathway is an important, dysregulated pathway in several tumor types, including pancreatic ductal adenocarcinoma. Although the activation of this pathway is an important component of normal development, its aberrant activation resulting from activating or inactivating mutations in the CTNNB1 gene locus, or in the negative regulators AXIN and APC involving stabilization of β-catenin, and activation of target genes leads to a more aggressive phenotype, suggesting its potential value as a therapeutic target in the treatment of pancreatic ductal adenocarcinoma. A number of small molecule and biologic agents have now been developed for targeting this pathway. This review summarizes the current knowledge about the therapeutic potential of targeting the Wnt pathway with particular emphasis on preclinical/clinical studies in the treatment of pancreatic ductal adenocarcinoma.
Wnt/β-连环蛋白信号通路在包括胰腺导管腺癌在内的多种肿瘤类型中是一条重要的、失调的信号通路。尽管该信号通路的激活是正常发育的重要组成部分，但其由于CTNNB1基因座的激活或失活突变，或涉及β-连环蛋白稳定化的负调节因子AXIN和APC的激活而导致的异常激活，以及靶基因的激活会导致更具侵袭性的表型，这表明其作为胰腺导管腺癌治疗靶点的潜在价值。目前已经开发了许多针对该信号通路的小分子和生物制剂。本综述总结了目前关于靶向Wnt信号通路治疗潜力的知识，特别强调了在胰腺导管腺癌治疗中的临床前/临床研究。
