Frizzled receptor and Wnt co-receptor (FZD/LRP)

Frizzled receptors (FZD1-10) are a family of Class F G protein-coupled receptors that, together with co-receptors such as LRP5 and LRP6, mediate the Wnt signaling pathway (PubMed: 22542152). This signaling axis is a master regulator of embryonic development, cell fate determination, and the maintenance of adult stem cell niches (UniProt: Q9H461). Aberrant activation of this pathway, frequently through mutations in downstream components like APC or through receptor overexpression, is a major driver in various cancers, including colorectal, breast, and hepatocellular carcinoma (PubMed: 28348298). Beyond oncology, mutations in Frizzled or its co-receptors are linked to bone density disorders and vascular eye diseases (NIH: Genetic Home Reference). Therapeutic strategies targeting these receptors include monoclonal antibodies like vantictumab and decoy receptors like ipafricept, which aim to inhibit tumor growth by blocking Wnt binding (PubMed: 25135992). However, because Wnt signaling is essential for normal tissue homeostasis, drug development faces significant challenges regarding on-target toxicities, particularly bone loss and intestinal damage (PubMed: 29079457).

Other names

Frizzled familyFZDLow-density lipoprotein receptor-related protein 5/6LRP5/6Wnt receptor complexClass F G protein-coupled receptors

Antagonism of Wnt ligand binding to Frizzled receptors or co-receptors to inhibit downstream beta-catenin stabilization and transcription of oncogenic target genes.