Targeting the Versatile Wnt/β-Catenin Pathway in Cancer Biology and Therapeutics: From Concept to Actionable Strategy

This expert review offers a critical synthesis of the latest insights and approaches at targeting the Wnt/beta-catenin pathway in various cancers such as colorectal cancer, melanoma, leukemia, and breast and lung cancers. Notably, from organogenesis to cancer, the Wnt/beta-catenin signaling displays varied and highly versatile biological functions in animals, with virtually all tissues requiring the Wnt/beta-catenin signaling in one way or the other. Aberrant expression of the members of the Wnt/beta-catenin has been implicated in many pathological conditions, particularly in human cancers. Mutations in the Wnt/beta-catenin pathway genes have been noted in diverse cancers. Biochemical and genetic data support the idea that inhibition of Wnt/beta-catenin signaling is beneficial in cancer therapeutics. The interaction of this important pathway with other signaling systems is also noteworthy, but remains as an area for further research and discovery. In addition, formation of different complexes by components of the Wnt/beta-catenin pathway and the precise roles of these complexes in the cytoplasmic milieu are yet to be fully elucidated. This article highlights the latest medical technologies in imaging, single-cell omics, use of artificial intelligence (e.g., machine learning techniques), genome sequencing, quantum computing, molecular docking, and computational softwares in modeling interactions between molecules and predicting protein-protein and compound-protein interactions pertinent to the biology and therapeutic value of the Wnt/beta-catenin signaling pathway. We discuss these emerging technologies in relationship to what is currently needed to move from concept to actionable strategies in translating the Wnt/beta-catenin laboratory discoveries to Wnt-targeted cancer therapies and diagnostics in the clinic.