Therapeutic potential of targeting wnt/ β-catenin -pathway in treatment of esophageal cancer

It has been reported that Wnt signaling pathway plays an important role in the carcinogenesis, progression, metastasis, and invasion of many cancer subtypes, including Esophageal Carcinoma. Theextensive investigations regarding the association of Wnt/β-catenin signaling with the progression of different cancers have led to developing the molecular targeted therapy. The aim of this study is to givean overview of the therapeutic potential of targeting Wnt/β-Catenin pathway with particular emphasis on studies in treatment of esophageal cancer.A literature search in multiple databases including thetherapeutic potential of targeting Wnt/β-Catenin pathway in ESCC was performed. The following keywords were used in combination: esophagus squamous cell carcinoma or ESCC and Wnt/β-Catenin Pathway or targeting Wnt/β-Catenin pathway .Wnt signaling pathway divided into two categories: canonical and non-canonical (β-catenin independent) signaling pathway. Wnt canonicalsignaling pathway plays a pivotal role in carcinogenesis and progression in ESCC. It has been reported that Wnt2 and β-catenin are upregulated, while GSK3β is downregulated in ESCC tissue. β-cateninoverexpression results in epithelial-to-mesenchymal transition (EMT) which would lead to tumor metastasis, thus Wnt/b-catenin signaling pathway inhibitors can reduce cell proliferation and tumor growth. Modified expression of TIP30, IL23, SOX10, SOX17, SALL4 genes which are involved in regulating β-catenin and Wnt signaling pathway, has reported in ESCC patients. Additionally, regulatory molecules such as miR-214, miR-518, miR-200b, air-ITCH can inhibit proliferation and invasion of esophageal squamous cell carcinoma, while mir638, miR-942, lncRNA MALAT1, lncRNA HOTAIR and RAP1B promote esophageal squamous cell carcinoma via targeting Wnt/β-Catenin Pathway. Wnt signaling pathway components are considered as potential targets for drug inhibition. The Wnt/β- catenin pathway Targeting might be a novel approach for ESCC treatment

Keywords:

Gene and Cancer , Cell and Cancer , Cancer Genetics , Cancer Treatment and Management , Targeted Cancer Therapy