FZD10 and Diseases: From Molecular Mechanisms to the Potential of Targeted Therapy

Frizzled class receptor 10 (FZD10) is a member of the Frizzled family of seven-transmembrane receptors. It mediates Wnt signaling through both canonical (β-catenin) and non-canonical (planar cell polarity and Ca²⁺) pathways, thereby regulating cell proliferation, differentiation, migration, apoptosis, and stem cell self-renewal. Dysregulation of FZD10-resulting from altered expression, aberrant promoter methylation, or functional impairment-has been linked to multiple human diseases, including cancers, metabolic and inflammatory disorders, and neurodegenerative conditions. In malignant tumors, FZD10 shows tissue-specific oncogenic activity. It is overexpressed in synovial sarcoma, colorectal cancer, gastric cancer, hepatocellular carcinoma, cervical cancer, ovarian cancer, nasopharyngeal carcinoma, non-small cell lung cancer, and renal cell carcinoma, but downregulated in esophageal squamous cell carcinoma. This restricted expression pattern makes FZD10 a potential biomarker for diagnosis and prognosis, as well as a candidate for targeted therapy. This review summarizes current knowledge on FZD10, covering its gene and protein structure, signaling mechanisms, and roles in various diseases. We also discuss its diagnostic and prognostic value in different cancers, and review recent progress in FZD10-targeted strategies, including antibodies, radioimmunotherapy, small-molecule inhibitors, drug repurposing, exosome-based delivery, and gene editing. Current limitations, such as the context-dependent functions of FZD10 and the safety issues associated with targeted agents, are also discussed. Future studies are needed to clarify the mechanistic basis of FZD10 action and to develop biomarkers for patient stratification.