Wnt/β-catenin Signaling Inhibitors

Zhang，Xun1; Dong，Nazhen2; Hu，Xiaoyan3,4

2023

10.2174/1568026623666230303101810

Current Topics in Medicinal Chemistry   Impact Factor & Quartile

1568-0266

1873-4294

The Wnt/β-catenin signaling pathway plays a crucial role in the development, tissue ho-meostasis, angiogenesis, and carcinogenesis of cancer. Mutations and excessive activation of the Wnt/β-catenin signaling pathway in cancer cells and cancer stem cells lead to drug resistance and recurrence of cancer in patients treated with conventional chemotherapy and radiotherapy. Upregu-lation of proangiogenic factors is persistently induced by hyperactivated Wnt/β-catenin signaling during tumor angiogenesis. Furthermore, mutations and hyperactivated Wnt/β-catenin signaling are associated with worse outcomes in several human cancers, including breast cancer, cervical cancer, and glioma. Therefore, mutations and hyperactivation of Wnt/β-catenin signaling create challenges and limitations in cancer treatment. Recently, in silico drug design as well as high-throughput as-says and experiments have demonstrated the promising anticancer efficacy of chemotherapeutics, such as blocking the cancer cell cycle, inhibiting cancer cell proliferation and endothelial cell angi-ogenesis, inducing cancer cell apoptosis, removing cancer stem cells, and enhancing immune re-sponses. Compared to conventional chemotherapy and radiotherapy, small-molecule inhibitors are considered the most promising therapeutic strategy for targeting the Wnt/β-catenin signaling path-way. Herein, we review the current small-molecule inhibitors of the Wnt/β-catenin signaling path-way, focusing on Wnt ligands, Wnt receptors, the β-catenin destruction complex, ubiquitin ligases and proteasomal destruction complex, β-catenin, β-catenin-associated transcriptional factors and co-activators, and proangiogenic factors. We describe the structure, mechanisms, and functions of these small molecules during cancer treatment in preclinical and clinical trials. We also review several Wnt/β-catenin inhibitors reported to exhibit anti-angiogenic effects. Finally, we explain various challenges in the targeting of the Wnt/β-catenin signaling pathway in human cancer treatment and suggest potential therapeutic approaches to human cancer.

Angiogenesis Cancer Cancer stem cells Drug resistance Inhibitors Therapeutic Wnt/β-catenin signaling

SCI

English

First

Pharmacology & Pharmacy

Chemistry, Medicinal

WOS:001029776300005

BENTHAM SCIENCE PUBL LTD

CHEMISTRY

2-s2.0-85163190630

Scopus

1.Department of Materials Science and Engineering,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
2.Department of Clinical Laboratory,Tianjin Beichen Hospital,Tianjin,300400,China
3.Institute of Biomedicine and Biotechnology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,518055,China
4.University of Chinese Academy of Sciences,Beijing,100864,China

Zhang，Xun,Dong，Nazhen,Hu，Xiaoyan. Wnt/β-catenin Signaling Inhibitors[J]. Current Topics in Medicinal Chemistry,2023,23(10):880-896.

Zhang，Xun,Dong，Nazhen,&Hu，Xiaoyan.(2023).Wnt/β-catenin Signaling Inhibitors.Current Topics in Medicinal Chemistry,23(10),880-896.

Zhang，Xun,et al."Wnt/β-catenin Signaling Inhibitors".Current Topics in Medicinal Chemistry 23.10(2023):880-896.