Electrochemical Biosensors for Cancer Diagnosis and Prognosis Using Protein Biomarkers: Current Trends, Advances, and Clinical Translation Potential

Cancer, a disease with high mortality, represents a major public health challenge. Increased access to early tumor screening, especially non-invasive liquid biopsy assays targeting blood-circulating protein biomarkers, has advanced cancer diagnosis and treatment, but these assays are still scarce. This work critically reviews general strategies for the rapid and accurate electrochemical detection of serum proteins and surveys recent advances in liquid biopsy electrochemical biosensors targeting cancer-related proteins. Many of these approaches have achieved remarkable analytical sensitivity. The review further addresses key barriers to clinical translation and commercialization, including complex sample matrix effects that require rigorous standardization of preanalytical and analytical workflows, limited validation using patient samples, difficulties in accounting for interpatient variability, and practical considerations such as manufacturability, cost-effective scale-up, and long-term stability. Accordingly, particular emphasis is placed on clinically translatable detection methods, with a focus on the analytical and clinical validation of biosensors.