Genes & Diseases · 19 authors, 9 centres
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This narrative review summarizes canonical and non-canonical Wnt signaling mechanisms, their roles in stem cell biology, and their association with diseases including cancer and bone disorders. The review highlights emerging therapeutics such as romosozumab and early-phase clinical trials targeting the Wnt pathway.
This narrative review synthesizes current knowledge on the Wnt signaling pathway, beginning with an overview of canonical (β-catenin-dependent) and non-canonical (β-catenin-independent) mechanisms. The review summarizes the role of Wnt signaling in self-renewal of embryonic, hematopoietic, mesenchymal, gut, neural, and epidermal stem cells, as well as in tumor cells with stem cell-like properties. Aberrant Wnt signaling is discussed in relation to a wide variety of diseases, including cancer, where mutations in Wnt pathway members can lead to unchecked cell proliferation, epithelial–mesenchymal transition, and metastasis. Wnt signaling is also highlighted as crucial for bone formation and as a potential therapeutic target for bone disorders. The authors note that romosozumab, a monoclonal antibody targeting sclerostin, illustrates therapeutic potential, and that multiple anti-cancer treatments targeting the Wnt pathway have entered early-phase clinical trials. A significant challenge identified is side effects on normal tissue, warranting further study of cancer-specific regulators of Wnt signaling.
