MUC1 as a diagnostic biomarker and siRNA-based therapeutic target in breast cancer: A clinical chemistry perspective.

Breast cancer remains the leading cause of cancer mortality in women, and early detection coupled with real-time monitoring of tumor burden are clinical imperatives; yet existing imaging-based screening (e.g., mammography, ultrasound) suffers from sensitivities as low as 60-80% and even lower in dense breasts plus substantial false-positive rates, underscoring the critical need for molecular assays with higher accuracy. Current clinical assays for circulating MUC1 (CA15-3) achieve high specificity but exhibit limited sensitivity in early-stage disease, underscoring a critical unmet need for more sensitive, multiplexed biomarkers to enable timely intervention. Mass spectrometry-based glycoproteomic workflows offer multiplexed quantification of tumour-associated MUC1 glycoforms, substantially improving analytical specificity and dynamic range. Complementary liquid-biopsy platforms that detect anti-MUC1 autoantibodies further extend lead time for recurrence detection. Concurrently, small interfering RNA (siRNA) therapies targeting MUC1 delivered via ionizable lipid nanoparticles demonstrate efficient tumor accumulation, robust mRNA knockdown, and favourable safety in phaseI solid tumor trials. In this review, we critically assess the analytical performance and standardization challenges of current MUC1 assays, evaluate emerging mass spectrometry and immunoarray techniques, and examine chemical and nanocarrier strategies that surmount biological barriers to siRNA delivery. We propose a co-development framework for harmonized companion diagnostics and MUC1-directed RNAi therapeutics under unified regulatory pathways, paving the way for precision, biomarker-driven interventions in breast cancer care.