MUC16. a large transmembrane glycoprotein belonging to the mucin family, is characterized by its extensive glycosylation and tandem repeat domains. It plays a critical role in cellular lubrication, signaling, and immune modulation. Clinically, MUC16 is best known as the antigen recognized by the cancer biomarker CA125. widely used for monitoring ovarian cancer progression and treatment response. Overexpression of MUC16 is strongly associated with malignancies, including ovarian, pancreatic, and breast cancers, where it promotes metastasis, immune evasion, and chemoresistance by interacting with mesothelin and galectins.
Antibodies targeting MUC16 have become essential tools in diagnostics and therapeutics. In diagnostics, anti-MUC16 antibodies underpin CA125-based immunoassays for cancer screening and recurrence detection. Therapeutically, engineered monoclonal antibodies (e.g., oregovomab), antibody-drug conjugates (ADCs), and CAR-T cells targeting MUC16 are under investigation. These therapies aim to disrupt tumorigenic pathways or deliver cytotoxic payloads specifically to MUC16-expressing cancer cells.
However, challenges remain due to MUC16's structural complexity, glycosylation heterogeneity, and potential shedding of extracellular domains, which may compromise antibody specificity and efficacy. Ongoing research focuses on optimizing epitope selection, enhancing antibody penetration, and overcoming immune tolerance. Advances in bispecific antibodies and combination therapies hold promise for improving outcomes in MUC16-associated cancers.