Therapeutic targeting of FZD receptor proteins with biologics in cancer

Wnt signaling plays key roles in the initiation, progression, and therapy resistance of various cancers. No drugs targeting this pathway are currently available, and several candidates have failed because they affected healthy tissues such as bone and intestine. It is necessary, therefore, to develop efficient and safe Wnt pathway inhibitors that act selectively on tumors. The targeting of individual FZD receptor proteins that initiate Wnt pathways is a promising approach to the development of selective inhibitors. In this review, we summarize the physiological and pathological roles of each of ten FZDs and describe diverse selective biologics that have been developed to target them. Antibodies, designer proteins, peptides, nanobodies, and aptamers are being studied for their potential as selective, efficient, and safe anti-Wnt treatments that could be used to combat specific cancers and other pathologies.