Advances in targeting the WNT/β-catenin signaling pathway in cancer

Abstract

WNT/β-catenin signaling orchestrates various physiological processes, including embryonic development, growth, tissue homeostasis, and regeneration. Abnormal WNT/β-catenin signaling is associated with various cancers and its inhibition has shown effective antitumor responses. In this review, we discuss the pathway, potential targets for the development of WNT/β-catenin inhibitors, available inhibitors, and their specific molecular interactions with the target proteins. We also discuss inhibitors that are in clinical trials and describe potential new avenues for therapeutically targeting the WNT/β-catenin pathway. Furthermore, we introduce emerging strategies, including artificial intelligence (AI)-assisted tools and technology-based actionable approaches, to translate WNT/β-catenin inhibitors to the clinic for cancer therapy.

Keywords: Artificial intelligence; Cancer; Challenges; Clinical trials; Drug design; Inhibitors; Natural products; Nuclear transport; Phase transition; Phosphorylation; Protein-small molecule interaction; Targeting protein-protein interaction; WNT/β-catenin signaling.