WNT Signaling in Disease

The document from August 3, 2019, reviews the WNT signaling pathway's role in a variety of human diseases, including cancer, Alzheimer's, metabolic syndrome, and others. It explains how mutations in WNT pathway components can lead to diseases, such as colorectal cancer, where about 80% of cases involve mutations in the APC gene. The review also discusses the potential of WNT signaling in aging and its effects on hair graying and bone healing. It highlights the complexity of WNT signaling, its crosstalk with other pathways, and the therapeutic potential of targeting this pathway. For instance, the document mentions the FDA-approved drugs vismodegib and erismodegib for basal cell cancers and a topical treatment, SM04554, in Phase II clinical trials for androgenetic alopecia that has shown increased hair follicle counts. The review underscores the importance of a balanced approach to manipulating WNT signaling in disease treatment, considering the "Goldilocks hypothesis" where the level of WNT signaling must be neither too high nor too low.